Dictionary of Pharmacology - A


A: a symbol used in pharmacokinetics to denote the amount of drug in the body usually expressed in mg or μmole.

A: slang term for amphetamine.

Aa: a symbol used in pharmacokinetics to denote the amount of drug at the absorption site remaining to be absorbed usually expressed in mg or μmole.

a priori: an event or experience which is known to be or can be deduced as being true or false without reference to any experience. That is, something deduced from prior knowledge rather than from experimentation.

A61603: a selective and potent α1A-adrenoceptor agonist.
Knepper SM et al. A-61603, a potent α1-adrenergic receptor agonist, selective for the α1A receptor subtype. J Pharmacol Exp Ther (1995) 274; 97

A23187: also known as calcimycin, an antibiotic which shows weak in vitro activity against gram-positive bacteria and some fungi. It is also a divalent cation ionophore commonly used to increase intracellular levels of calcium ions in intact cells. It is known to uncouple oxidative phosphorylation and to inhibit mitochondrial ATPase. It has been shown to induce apoptosis in some cells and block it in others.
Boot JH and Van Hilten JA. The use of the divalent calcium-ionophore A23187 as a biochemical tool in pharmacological and in vitro toxicological studies. Cell Struct Funct (1996) 21; 97-99

A71623: a substituted tetrapeptide and selective cholecystokinin CCKA agonist. It causes suppression of appetite, decreases food intake and has been used as a pharmacological tool in investigations of anorexia.
Asin KE et al. Behavioral effects of A71623, a highly selective CCK-A agonist tetrapeptide. Am J Physiol (1992) 263; R125-35

α1-Antitrypsin: also known as AAT, a naturally occurring 52kDa serine protease (also known as a serpin) of the α1-globulin class and the principal serum inhibitor of proteolytic enzymes such as neutrophil elastase. It protects tissues from the effects of enzymes from inflammatory cells especially elastase. A deficiency of AAT causes pulmonary emphysema and liver disease.

α1-Antitrypsin deficiency: is a common and lethal hereditary disorder characterized by reduced serum levels of α1- antitrypsin, a 52kDa glycoprotein synthesized mainly in the liver, macrophages and neutrophils. α1-antitrypsin acts as an anti-protease and inhibits neutrophil serine proteases such as neutrophil elastase, cathepsin G and proteinase 3. α 1 -Antitrypsin deficiency is mainly observed in the lung with a high risk of emphysema occurring by the third or fourth decade of life in individuals affected.
AAT: α1-antitrypsin

ABC transporters : ATP binding cassette transporters are a superfamily of membrane-bound proteins present in bacteria and human cells which use ATP to actively pump out drugs from the cytoplasm. They are responsible for multidrug resistance of bacterial and tumour cells. Examples of ABC transporters include P-glycoprotein and MRP (multidrug resistance protein).
Polgar O, Bates SE. ABC transporters in the balance: is there a role in multidrug resistance. Biochem Soc Trans (2005) Feb: 33(Pt 1); 241-5

Abciximab: also known a s C7E3 Fab, a chimeric (murine/human) monoclonal antibody Fab fragment which binds specifically to the glycoprotein complex GPIIb/IIIa which is expressed on the surface of platelets. Abciximab is a platelet aggregation inhibitor which has been used to prevent thrombosis in high risk patients undergoing coronary angioplasty as an adjunct to heparin and aspirin.
Foster RH, Wiseman LR. Abciximab. An updated review of its use in ischaemic heart disease. Drugs (1998) 56; 629-65

Abdominal stretch assay: a test to determine the efficacy of analgesic agents in which an animal, usually a mouse, is injected intraperitoneally with an irritant such as acetic acid (in an acetic acid writhing assay) or phenylquinone. The number of contractions of the abdomen, extensions of the hind limbs and twists and turns of the abdomen are counted. An analgesic given prior to injection of an irritant decreases the number of writhings and its analgesic actions can be measured by the decrease in the number of writhings where a potent analgesic causes a marked decrease in movements. This test is commonly used in screening for analgesic activity due to its simplicity and sensitivity but lacks specificity and there is a wide difference in response according to animal strain.

Ablukast: also known as Ro 23-3544, a benzopyran derivative, LTC4 leukotriene receptor antagonist and a platelet aggregation inhibitor with some anti-asthmatic actions.
O'Donnell M et al. Pharmacological profile of Ro 23-3544, a new aerosol active leukotriene receptor antagonist. Adv Prostaglandin Thromboxane Leukot Res. (1987) 17A:512-8

AB- MECA: an A3 adenosine receptor ligand (4-aminobenzyl-5 N-methylcarboxamidoadenosine) available in radio-iodinated form for adenosine receptor studies.
Olah ME et al. 125I-4-aminobenzyl-5'-N-methylcarboxamidoadenosine, a high affinity radioligand for the rat A3 adenosine receptor. Mol Pharmacol (1994) 45(5); 978-8

Abnormal base analogue: an exogenous (and usually synthetic) analogue of a DNA or RNA base. They can be incorporated into replicating nucleic acids where they produce lethal mutations by causing mispairing which in turn leads to inhibition of cell division and many were originally developed as anticancer agents because of this property. These compounds are highly cytotoxic to both cancerous and normal cells and are highly mutagenic. They therefore have low therapeutic indexes. Examples include 5-bromouracil, 2-aminopurine, 5-fluorouridine and 6-mercaptopurine which all inhibit the cell cycle.

Abortifacients: also known as interceptives and contragestational drugs, compounds which cause abortion or miscarriage of a foetus before the stage of viability. A variety of compounds have historically been used as interceptives and contragestational drugs including quinine, urea, ergometrine and metergoline. More commonly, mifepristone (a progestogen antagonist), the prostaglandins gemeprost and dinoprostone have also been used.

Abrin: also knows as toxalbumin and agglutinin, a cytotoxic lectin and haemagglutinin comprising two peptide chains linked by a disulphide bridge and having more than 30 variant forms. It can be obtained from the seeds of jequirity (Abrus precatorius) and the seed of the rosary pea (Abrus precatorius). It is an inhibitor of ribosomal protein synthesis in intestinal cells which causes cell death. Ingestion causes diarrhoea and loss of blood in the stool and can cause cerebral edema and cardiac arrhythmias. It is used experimentally against tumours and pathogenic microorganisms.

AC187: also known as acetyl-[Asn30,Tyr32]-salmon calcitonin8-32, a selective amylin receptor antagonist which may be of use in the development of therapy for Alzheimer's disease by inhibiting the deposition of the neurotoxic excitatory peptide amylin. Amylin also has vascular actions.
Beaumont K et al. Differential antagonism of amylin's metabolic and vascular actions with amylin receptor antagonists. Can J Physiol Pharmacol (1995) 73(7); 1025-9

ACAC: acetyl coenzyme-A carboxylase

Acadesine: also known as AICA riboside and GP1-110, an adenosine regulating agent, a purine nucleoside analogue (it is 5-aminoimidazole-4-carboxamide riboside) and purine precursor which has cardioprotective effects. It is pharmacologically inactive under normal circumstances but is active under conditions of net ATP catabolism such as in myocardial ischaemia. It may cause the release of adenosine which in turn inhibits platelet aggregation and has an antiarrhythmic action. Acadesine has been shown to stimulate anaerobic glycolysis in heart tissue and has been shown to cause sustained functional protection against injury during periods of ischaemia and reperfusion in animals.
Mullane K. Acadesine: the prototype adenosine regulating agent for reducing myocardial ischaemic injury. Cardiovasc Res (1993) 27(1); 43-7

Acamprostate: a GABA receptor agonist related to taurine. It has been used in the treatment of alcohol dependence and may be of use as a neuroprotectant.
Pelc I et al. The European NEAT program: an integrated approach using acamprostate and psychosocial support for the prevention of relapse in alcohol-dependent patients with a statistical modeling of therapy success prediction. Alcohol Clin Exp Res (2002) 26(10); 1529-38

Acarbose : also known as Bay g 5421 and a-GHI, a oligosaccharide from microorganisms of Actinoplanes sp. An inhibitor of saccharases and an a-glucosidase inhibitor which reduces the breakdown and absorption of carbohydrates in the intestine (such agents are also known as starch blockers). It is used in the treatment of diabetes to control body weight in type 2 diabetic patients, ie individuals with non-insulin dependent diabetes mellitus also known as maturity onset diabetes showing insulin resistance and impaired regulation of insulin secretion. Acarbose delays carbohydrate absorption and diminishes a postprandial increase in blood glucose.
Clissold SP, Edwards C. Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs (1988) 35(3); 214-43

Acaricides: (not to be confused with ascaricides) also known as miticides and scabicidal agents, these are agents which specifically kill mites and ticks particularly phytophagous mites as opposed to parasitic mites. Some mites cause local irritation such as scabies caused by the itch mite Sarcoptes scabiel and others carry diseases such as Lyme disease and typhus. Acaricides comprise a diverse group of compounds and include halogenated hydrocarbons such as dieldrin and lindane, organophosphorus compounds such as malathion, pyrethroids such as permethrin and phenothrin, carbamates such as carbaryl and some miscellaneous compounds including diclofonal, benzylbenzoate, crotamiton, monosulfiram and chlorbenzilate. Most of these compounds are formulated into creams and ointments for topical application. They show a variety of mechanisms of action including cholinesterase inhibition (malathion) and some cause instability and stimulation of the insect nervous system (lindane and dieldrin).

ACAT: acyl-coenzyme A cholesterol acyltransferase

Acceptable daily intake (ADI): the amount of an environmental chemical (usually pesticides and food additives) which humans can ingest each day throughout their lives without the occurrence of appreciable adverse effects. ADI is expressed in mg/kg/day and is used in the assessment of risks posed by food additives, pesticide residues and environmental contaminants. These levels are set by WHO in association with national agencies such as the Environment Protection Agency in the US and the Advisory Committee on Pesticides and Other Toxic Chemicals in the UK.

Acceptor site: the site, usually in a receptor or enzyme, to which the ligand attaches but which does not mediate the biological effects of the ligand.

ACE: angiotensin converting enzyme
Acebutolol: a β2 subtype-selective adrenoceptor antagonist (N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butamide) with some intrinsic a 1-partial agonist activity) use in the treatment of angina, arrhythmias (Class II antiarrhythmic) and hypertension.
Giacomini JC, Thoden WR. Ancillary pharmacologic properties of acebutolol: cardioselectivity, partial agonist activity, and membrane-stabilizing activity. Am Heart J (1985) 109; 1137-44


Aceclidine: an acetoxyquinuclidine analogue (3-quinuclidinyl acetate), a muscarinic agonist and cholinesterase inhibitor. It has been used in the treatment of glaucoma and shows hypotensive effects.
Ehlert FJ et al. The interaction of the enantiomers of aceclidine with subtypes of the muscarinic receptor. J Pharmacol Exp Ther (1996) 279; 1335-44

Acedapsone: also known as DADDS, a sulphone antimalarial and antileprotic.
Neelan PN et al. Limited duration acedapsone prophylaxis in leprosy, Indian J Lepr (1986) 58; 251-6

Acetazolamide: a potent carbonic anhydrase inhibitor (N-(5-)aminosulphonyl)-1,3,4-thiadiazo-1,2-yl)acetamide) which is used as a diuretic (although it is a weak diuretic and not a drug of choice). It can be used to treat seizures such as atypical absence, atonic and tonic seizures glaucoma.

Acetaminophen: an analgesic and antipyretic compound (N-(4-hydroxyphenyl)acetamide) available over the counter in many preparations such as paracetamol in the UK and Tylenol in the US for the treatment of pain and inflammation (although it may only have weak anti-inflammatory effects).


It is a cyclooxygenase inhibitor possibly selective for COX-3 which is only expressed in the brain and spinal cord. Acetaminophen is hepatotoxic at high doses as it is metabolised to a hepatotoxic intermediate by cytochrome P450 in the liver. It has been used as a pharmacological tool to induce liver damage. Acetaminophen was first prepared in 1878.
Rahman TM, Selden AC, Hodgson HJ. A novel model of acetaminophen-induced acute hepatic failure in rabbits. J Surg Res (2002) 106(2); 264-72

Acetic acid-induced colitis: an animal model of colitis used to investigated the anti-inflammatory and/or mucoprotectant effects of test compounds. Typically, an enema of about 1ml of a 4% solution of acetic acid is introduced directly in to the colon 24 hours before administration of the test compound. Colonic inflammation by acetic acid is characterized by gross and microscopic injury, bowel wall thickening, cessation of fluid absorption, glutathione depletion, increased leukotriene B4 synthesis with increased levels of myeloperoxidase and alkaline phosphatase activities. Ulcers may appear in the colon if a higher concentration of acetic acid, eg 10% is used. Examination of the colon is usually by colonoscopy.

Acetic acid writhing assay: a form of abdominal stretch assay used to test the effects of analgesic (antinociceptive) compounds. Writhing is observed in experimental animals following injection of acetic acid into their abdomen. Typically, a 1-3% solution of acetic acid is injected intraperitoneally into mice about 30 minutes after administration of the compound being tested for analgesic effects (or about 120 minutes after oral administration of test compound) and the number of times the animal shows abdominal writhings is counted. A decrease in the number of writings indicates an analgesic effect where the extent of the decrease roughly indicates the potency of analgesia.
Koster et al. Acetic acid for analgesic screening. Fed Proc (1959) 18; 412

Acetylator phenotype: an individual pharmacogenetic variation in the expression of N-acetyltransferase isoforms which is related to how quickly individuals acetylate drugs and detoxify them (if the principal route of metabolism is acetylation). Acetylator phenotypes are generally divided into two groups, ie fast and slow acetylators and their phenotype can markedly influence how drugs are prescribed for them because of the rate at which they metabolize drugs.

Acetyl coenzyme-A carboxylase (ACAC): an enzyme ( EC ) involved in the synthesis of fatty acids from coenzyme A and which is present in both animals and plants. It catalyses the formation of malonyl-CoA from acetyl CoA and, as it is the first enzyme in this pathway, is an important enzyme in lipid metabolism. Its activity is regulated by phosphorylation and dephosphorylation, the cellular levels of palmitoyl CoA and indirectly by the effects of glucagon and adrenaline.

Acetyl coenzyme-A carboxylase inhibitors: compounds which inhibit acetyl coenzyme-A carboxylase and so lower blood levels of fatty acids and lower blood triglycerides levels. Examples include nafenopin.

Acetylcholine (ACh): the choline ester of acetic acid and a excitatory neurotransmitter found in cholinergic neurones throughout the central and peripheral nervous systems of vertebrates. It is also present in peripheral sites including neuromuscular junctions, preganglionic neurones, parasympathetic postganglionic neurones and some postganglionic sympathetic neurones. Acetylcholine is synthesized in nerve terminals from choline and acetyl CoA by the mitochondrial enzyme choline acetyltransferase.


(Quarternary ammonium compounds contain the positively charged polyatomic moiety of the structure NR4+.)
The effects of acetylcholine are classified into two groups. Nicotinic effects (which are mimicked by nicotine) at acetylcholine receptor sites present on the post-synaptic membranes of autonomic ganglion cells, in the endplates of skeletal muscle cells and in the adrenal medulla. Muscarinic effects (which are mimicked by muscarine) at acetylcholine receptor sites in effector organs which are innervated by post-ganglionic cholinergic nerves. These sites are the heart, smooth muscle and exocrine glands.
At small doses ACh produces the same effects as muscarine, ie a fall in blood pressure due to vasodilation, slowing of the heart rate, increases in the contraction of smooth muscle in many organs and increased secretions from exocrine glands. Large doses of ACh cause a rise in blood pressure which is the same effect as seen for nicotine.
Acetylcholine was first identified in 1914 by Henry Dale and later confirmed to function as a neurotransmitter by Otto Loewi.

Acetylcholine chloride: the chloride salt of acetylcholine and a muscarinic receptor agonist, cardiac depressant, peripheral vasodilator and hypotensive. It has been used as a miotic.

Acetylcholine releasing agents: compounds which cause the release of acetylcholine from nerve terminals and which include linopridine and bespiridine, black widow spider venom and β-bungarotoxin. Some of these have been investigated for potential use in dementia but have shown poor clinical efficacy.

Acetylcholine receptors: receptors for acetylcholine present in the central and peripheral nervous systems and divided into two subtypes, nicotinic and muscarinic, which are further divided into subtypes. Nicotinic and muscarinic receptors differ in the way they transmit signals across cell membranes and into the cell and are derived from two distinct gene superfamilies. See http://www.iuphar-db.org/GPCR/ChapterMenuForward? chapterID=1271

Acetylcholinesterase (AChE): a cholinesterase.

Acetylcholinesterase inhibitors (AChEI) : inhibitors of acetylcholinesterase, the main enzyme breaking down acetylcholine and thus terminating its actions. These inhibitors are divided into reversible inhibitors and irreversible inhibitors. Both types prolong the action of ACh and enhance neuromuscular transmission in voluntary and involuntary muscle. Excessive doses of either type can cause severely impair neuromuscular transmission and lead to cholinergic crises where depolarising block occurs.
- Reversible inhibitors, which include physostigmine, neostigmine, pyridostigmine, tacrine and velnacrine, either bind to AChE with greater affinity than ACh but do not react with the enzyme as a substrate would or are substrates for AChE, form an acetylated or carbamylated enzyme complex but undergo hydrolysis and are broken down to inactive or largely inactive components. Some reversible inhibitors are used clinically to treat myasthenia gravis. Tacrine has been used to enhance cerebral ACh transmission in the treatment of cognitive disorders such as Alzheimer's disease.
- Irreversible inhibitors, which include diisopropylfluorophosphate, ecothiophate and anatoxin-a(s), bind to AChE but esterify the enzyme to form phosphate esters. These undergo hydrolysis far more slowly than acetylated or carbamylated enzyme complex and are referred to as irreversible. Diisopropylfluorophosphate and ecothiophate have been used clinically as miotics although they are no longer the drugs of choice. Other irreversible AChEI have been used in chemical warfare as they cause muscle paralysis in high doses. Examples include sarin. A common application of these inhibitors is as insecticides.

Acetylcholinesterase stimulant: a compound which stimulates the actions of acetylcholinesterase and so increases the metabolism of acetylcholine.

Acetylsalicylic acid: aspirin

ACh: acetylcholine

AChEI: acetylcholinesterase inhibitor

Acid: common (street) name for lysergic acid diethylamide.

Acidosis: a condition in which the pH of the blood becomes more acidic than it usually is. It can result in the increased metabolism of some drugs where the metabolite is acidic.

Acid phosphatase: a lysosomal acid hydrolase which hydrolyses phosphoric acid esters. It is an important enzyme in the absorption and metabolism of nucleotides, phospholipids and carbohydrates. Serum levels of this enzyme have been used diagnostically as it is commonly elevated in cases of metastatic prostate cancer, Paget's disease and some metastases.

Aciclovir (acyclovir): also known as acycloguanosine, a synthetic, orally active acyclic nucleoside and guanine-derived antiviral compound (2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one).


It is active against Varicella zoster and herpes virus where it is mono- then triphosphorylated by herpes-specific thymidine kinase. This results in the formation of acyclo-GTP which inhibits viral DNA polymerase (about 30 times) more potently than it does cellular DNA polymerase thus preventing DNA replication and showing few side effects on host cells. Acyclo-GTP is also incorporated into viral DNA chains causing termination of strand elongation. Aciclovir is used clinically to treat Herpes simplex and Herpes zoster virus infections. Valaciclovir is its ester prodrug of aciclovir which is converted to aciclovir by the target virus and is a more potent antiviral.

Aclacinomycins: a family of antineoplastic antibiotics obtained from the bacteria Streptomyces galilaeus. These are two major components, aclacinomycins A and B. Aclacinomycin A (also known as aclarubicin) has anticancer activity against both solid tumours and leukaemias and may act by stabilizing topoisomerase I covalent complexes thus functioning as a topoisomerase I/II inhibitor.

Aconitine: also known as monkshood, a toxic diterpenoid alkaloid (16-ethyl-1,16,19-trimethoxy-4-(methoxymethyl)aconitane-3,8,10,11,18-pentol 8-acetate 10-benzoate) and neurotoxin obtained from the roots of monkshood or wolfsbane and other plants of Aconitum sp. It is used to induce cardiac arrhythmias and bradycardia in animal models of heart disorders. Aconitine is a sodium channel opener and inhibits the repolarization of myocardial cell membranes leading to repeated firing. It has positive inotropic effects on heart muscle and causes arrhythmias and was once used in the form of a tincture as a diaphoretic to treat fever although it is too toxic and is now obsolete. It is used, however, as a pharmacological tool to investigate acetylcholine mechanisms in the brain as it may also increase spontaneous acetylcholine release from the cerebral cortex. The ancient Greeks used it as an arrow poison.
Gutser UT et al. Mode of antinociceptive and toxic action of alkaloids of Aconitum spec. Naunyn Schmiedebergs Arch Pharmacol (1988) 357; 39-48

Aconitum alkaloids: a group of terpene alkaloids some of which are very poisonous obtained from Aconitum species. A good example is aconitine.

Acoustic priming: an effective method for inducing seizures in animals with a predisposition to seizures. Repeated acoustic stimuli from an early age induce audiogenic seizures after 6 weeks or so. These seizures can be used to test the effects of anti-epileptic drugs.

Acoustic startle: a type of startle reflex.

Actaplanins : a complex of glycopeptide, broad-spectrum, gram-positive antibiotics produced by Actinoplanes missouriensis. Six components are known, ie actaplanins A, B1, B2, B3, C1 and G and have been used to promote growth (ie, as veterinary growth stimulants) and to increase milk yields in ruminants chiefly in the US.

ACTH: adrenocorticotrophin

Actinomycins: a group of related antineoplastic antibacterial compounds produced by Streptomyces parvullus. Actinomycin D produces chromosomal breaks and translocations by intercalating in double-stranded DNA between deoxyguanine residues with its peptide side chains fitting into the minor groove of DNA.

Actinonin: a microbial metabolite and an aminopeptidase N inhibitor. It is used as a pharmacological tool in the study of anticancer compounds. Actinonin may inhibit the actions of peptide deformylasesand, as it appears to increase the production and secretion of neutrophil-activating peptides which activate human neutrophils. It may have anti-inflammatory actions.

Active oxygen: also known as singlet oxygen, this is a highly reactive state of oxygen and is produced from the reduction of triplet state divalent oxygen or spin inversion to the singlet state. It is an important molecule in the oxygen-dependent killing of microorganisms.

Active avoidance: a method used in the investigation of memory in which an animal is exposed to a noxious stimulus such as footshock and then re-exposed at a later time to see if it can actively avoid the stimulus (active avoidance) or not. This method is used to test the effects of drugs which improve memory.

Active site: also known as active centre, part of an enzyme to which the substrate specifically binds and in which catalysis take place. The structure of the active site determines which substrates bind and the nature of the catalysis. Alterations in the configuration of the active site often lead to an increased rate of reaction and changes in substrate specificity in genetically modified enzymes.

Active transport: an energy-requiring processes which permit the passage of molecules across membranes that would naturally act as barriers against their movement because of their size, charge or lipophilicity. There are two main types of active transport; primary in which energy is directly coupled to the movement of substance to cross a membrane independent of any other species, and secondary which transports one species across a membrane to drive the transport of another.

Activated charcoal: pyrolysed charcoal which has been treated with high-temperature steam of air to make it an absorbent. It has been used as an oral absorbent in cases of intoxication of a variety of substances such and is known to lower lipid absorption when given orally.

Acyl-CoA cholesterol acyltransferases (ACAT): also known officially as sterol O-acyltransferases, a group of two enzymes (ACAT1 and ACAT 2) (EC located on the cytoplasmic surface of liver endoplasmic reticulum and intestines which acylates cholesterol to form cholesteryl esters - the main storage form of cholesterol in cells. Cholesterol esters accumulate in the atheromatous plaques observed in major arteries and lead to the formation of atherosclerosis, a major death cause in Western industrialized countries. In humans, the absorption of dietary cholesterol and cholesterol ester accumulation is significantly reduced by the inhibition of intestinal ACAT activity.

Acyl-CoA cholesterol acyltransferase (ACAT) inhibitors: compounds which inhibit the cholesterol storage enzyme acyl-CoA cholesterol acyltransferase. These compounds have been developed for the inhibition of accumulation of cholesterol esters in the treatment of hyperlipidemia and hypercholesterolemia. Examples include the statins (eg pravastatin, lovastatin and simvastatin). It is thought that selective inhibition of ACAT2 may prove to be beneficial in the reduction of plasma lipoprotein cholesterol levels.
Ansell B. Future directions in lipid therapies. Adv Ther (2002) 19(2); 61-72

ADA: adenosine deaminase

ADC: antibody-drug conjugate designed to direct a cytotoxic drug towards cells expressing a cell-surface antigen which is specifically recognised by an antibody and used in cancer chemotherapy.
Polakis P. Antibody Drug Conjugates for Cancer Therapy. Pharmacol Rev. 2016 Jan; 68(1): 3-19.

Ademethionine: also known as S-adenosylmethionine, a compound which is a ubiquitous metabolite and which serves as a methyl donor in a large number of methylation reactions involving proteins, phospholipids, catecholamines and DNA.

Add-on therapy: therapy using a drug which is intended to supplement the effects of the principal agent which is only partially effective for the target disorder. Sometimes referred to as an adjuvant drug.

Additive response: a drug response where the effect of co-administering two or more agents causes neither synergism nor antagonism. That is, the overall response to the combination of drugs is equal to the effect of each drug when given separately assuming the same doses are used.

Addiction: has been defined as a state of periodic or chronic intoxication, detrimental to the individual and to society, produced by the repeated administration of a drug: its characteristics are a compulsion to continue to take the drug and to increase the dose, with the development of psychic and sometimes physical dependence on the effects of the drug, so that the development of means to continue the administration of the drug becomes an important motive in the addict's existence. All drugs to which addiction develops cause euphoria and a sense of well being. Examples of the many addictive drugs available include heroin, cocaine, tobacco and alcohol.

Address-message concept: used to refer to a molecule which comprises a binding site (address) and a site which confers biological activity (message) to the receptor molecule.

Adenohypophysis: the anterior part of the pituitary gland (hypophysis) which secretes a variety of hormones in response to the effects of releasing factors secreted by the hypothalamus.

Adenosine: a purine nucleoside present in all human cells mainly as a by-product of ATP metabolism. It is released into extracellular spaces under physiological and pathophysiological conditions characterized by increased oxygen demand/supply ratio. Adenosine exerts a wide spectrum of effects in various organs and tissues. It has central and pharmacological actions including vasodilation, inhibition of platelet aggregation, blockade of cardiac AV conduction, bronchoconstriction, mast cell stabilization, stimulation of nociceptive afferent neurones and neuroprotection. Adenosine is used in the treatment of paroxysmal supraventricular tachycardia where it is nearly 100% effective in terminating certain types of tachycardias and as a vasodilator in cardiac imaging. Although most ventricular tachycardias are insensitive to adenosine, this nucleoside is effective in ventricular tachycardia induced by catecholamines or exercise.
Pelleg A and Porter RS. The pharmacology of adenosine. Pharmacotherapy (1990) 10; 157-74

Adenosine deaminase (ADA): an enzyme (EC essential in the cellular metabolism of purines which deaminates adenosine and 2'-deoxyadenosine to inosine or 2'-deoxyinosine. ADA deficiency has been identified as forming the metabolic basis for 20-30% of cases with recessively inherited severe combined immunodeficiency (SCID).

Adenosine deaminase inhibitor : compounds which inhibit adenosine deaminase and so inhibiting the cellular metabolism of purines. Examples include pentostatin (2'-deoxycoformycin, dCF), a purine nucleoside analogue and fermentation product of Streptomyces antibioticus which has anticancer actions.

Adenosine kinase: an enzyme (EC which catalyses the phosphorylation of ribofurnosyl-containing nucleoside analogues at the 5'-hydroxyl using ATP or GTP as the phosphate donor. It is the most abundant nucleoside kinase in mammals.

Adenosine kinase inhibitors: inhibitors of adenosine kinase and compounds which inhibit the production of adenosine. Adenosine exhibits potent anti-inflammatory activities and adenosine kinase inhibitors have potent anti-inflammatory effects in vitro and in vivo. Examples include 5'-amino-5'- deoxyadenosine and iodotubericidin.

Adenosine uptake inhibitors: compounds which block the uptake of adenosine by purinergic neurones. Examples include dilazep which is a coronary, cerebral vasodilator and a suppressor of the effects of ischaemia.

Adenosine receptors: also known as P1 purinoceptors, P1 purine receptors, nucleoside receptors and P1 receptors, extracellular receptors which mediate a wide variety of mainly inhibitory effects such as bradycardia, vasodilation, platelet aggregation inhibition and slowing of peristalsis. There are four adenosine receptor subtypes (A1, A2A, A2B, and A3) which are G-coupled seven-transmembrane receptors with relatively short amino acid sequences and are linked to stimulation of inhibition of adenylyl cyclase.
Below is a list of adenosine agonists and antagonists with their receptor subtype selectivity. An asterisk denotes that the compound is selective or largely selective.
A1 agonist adenosine, cyclopentyladenosine, IB-MECA, NECA 1,3-dipropyl-8-phenylxanthine*, DPCPX, CGS 15943 A2A agonist adenosine, CGS 21680*, NECA antagonist ZM 241385*, CGS 15943 A2B agonist adenosine< antagonist MRS 1706, CGS 15943 adenosine, IB-MECA*, 2-Cl-IB-MECA*, NECA, HEMADO antagonist MRS 1220*

Fredholm BB et al. International Union of Pharmacology. Nomenclature and Classification of Adenosine Receptors. Pharmacological Reviews. (2001) 53(4); 527-552
Koltz. Adenosine receptors and their ligands. Naunyn-Schmied Arch Pharmacol (2000) 362; 382
http://www.iuphar- db.org/GPCR/ChapterMenuForward?chapterID=1273

Adenosine receptor agonists: compounds which activate adenosine receptors. Adenosine itself has inhibitory effects at A1 sites and produces drowsiness, motor incoordination and analgesia.

Adenosine receptor antagonist: compounds which block adenosine receptors. Examples include methylxanthines which have been used to treat asthma as they are A1 antagonists. Caffeine produces arousal and alertness by antagonising A2 receptors.

Adenylate cyclase: also known as adenylyl cyclase and adenyl cyclase, an enzyme (EC ) which catalyses the conversion of ATP to cAMP.

ADEPT: antibody-directed enzyme prodrug therapy

ADH: antidiuretic hormone

Adhesion molecules: also known as cell adhesion molecules (CAM) and intracellular adhesion molecules (ICAM), glycoproteins expressed on cell surfaces which are responsible for cells adhering to one another or to other cell types such as endothelial cells. They are essential in cell growth, differentiation, embryogenesis, immune cell migration and response and cancer cell metastasis. Adhesion molecules such as sialyl Lewis X, VCAM, selectins and integrins play essential roles in inflammation, for example, when cells of the immune system accumulate at the sites of inflammation.

Adhesion molecule inhibitors: also known as adhesion molecule antagonists, compounds which inhibit the effects of adhesion molecules and so inhibit inflammation and tumour cell metastasis.

Adhesion molecule synthesis inhibitors: compounds which inhibit the cellular synthesis of adhesion molecules and so inhibit cell to cell adhesion. They are being developed to treat cancer metastasis, inflammation and multiple sclerosis. Examples include natalizumab, a monoclonal antibody which recognizes VLA-4 and interferes with T cell migration into the CNS. It has been used clinically to treat relapsing-remitting multiple sclerosis.

ADI: acceptable daily intake

Adiponectin: also called GBP-28, apM1, AdipoQ and Acrp30, an adipose tissue-specific protein which is structurally related to collagen VIII and X and complement factor C1q and which is present in human plasma at high levels. A decrease in adiponectin expression has been shown to be related to insulin resistance in some animal models and its administration is accompanied by a reduction in plasma glucose concentrations and an increase in cellular insulin sensitivity. Adiponectin appears to play a protective role in animals models of vascular injury so is being investigated in the pathology of diabetes and related vasculopathies.
Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol (2003) 148(3); 293-300

Adipose tissue: fat storage tissue and a major endocrine organ. White adipose tissue is known to secrete a number of peptide hormones including leptin, cytokines, adipsin, acylation-stimulating protein, angiotensinogen, plasminogen activator inhibitor-1, adiponectin and resistin amongst others. It plays an important role in the regulation of appetite and sugar and fat metabolism.
Guerre-Millo M. Adipose tissue hormones. J Endocrinol Invest (2002) 25(10); 855-61

Adipsin: also known as complement factor D and ADN, a serine protease secreted by adipocytes such as those in white and brown fat. Several animal models of obesity show a deficiency in adipsin.

Adjuvant: a compound or substance which is added to another to enhance or speed up its effects particularly an immune reaction. An example is Freund's adjuvant which is used to enhance the immune reaction to antigens.

Adjuvant arthritis: a form of experimental arthritis caused by the local injection of an adjuvant such as a bacteria and method used to test the effects of anti-inflammatory agents. Typically, an injection of 0.1 ml of killed Mycobacterium butyricum (10mg/ml) in mineral oil into the paw of a rat will cause an inflammatory swelling.

Adjuvant-induced polyarthritis: a form of arthritis in which an adjuvant such as Freud's complete adjuvant is used to induce joint inflammation in an animal. This model is used to investigate the effects of anti-inflammatory drugs.

Adjuvant peptide: also known as muramyl dipeptide, an N-acetylmuramyl dipeptide and an essential component of mycobacterial cell walls.

ADME: absorption, distribution, metabolism and elimination; the principle processes determining the pharmacokinetic profile of a drug.

ADR: adverse drug reaction

Adrenal gland: also known as the suprarenal gland due to its position just above the kidneys, a triangle-shaped endocrine gland comprising two layers (the inner medulla and outer cortex) which secrete a variety of hormones. The medulla is comprised of chromaffin cells which secrete adrenaline and noradrenaline and the cortex produces androgens and testosterone as well as mineralocorticoids and glucocorticoids such as aldosterone and cortisol.

Adrenaline: also known as epinephrine in the US and worldwide, a chemical neurotransmitter (4-[1-hydroxy-2-(methylamino)-ethyl]-1,2-benzenediol) and hormone produced in the adrenal medulla. Adrenalin (without the e) is actually a trade name originally registered to Parke-Davis and Company but the name is in wide-spread use. It is an sympathomimetic amine which causes bronchodilation, vasoconstriction, CNS stimulation and mydriasis. Adrenaline has been used to stimulate the heart in cardiac failure and its actions are mediated by adrenoceptors. Adrenaline was first isolated and identified by John Abel in 1897. Adrenaline biosynthesis is outlined below.

adrenaline synthesis

Adrenergic: relating to the actions of adrenaline. This term is used to describe nerves, synapses and mechanisms of nerve conduction although noradrenergic is more appropriate in most cases as noradrenaline is actually the transmitter. Adrenergic neurones exist in the central nervous system.

Adrenergic neurone blocker: a compound which prevents the release of noradrenaline from sympathetic nerves. They are used as antihypertensives. Examples include guanadrel, guanethidine and debrisoquine.

Adrenergic transmitter depletors: compounds which deplete the levels of stored adrenergic transmitter in synapses. Examples include reserpine and deserpidine.

Adrenoceptors: also known as adrenoreceptors, a family of membrane-bound receptors present throughout both neuronal and non-neuronal mammalian tissue and which mediate a diverse range of responses to endogenous catecholamines, ie adrenaline and noradrenaline. They are divided into α and β receptors and further subdivided according to location and function.
   They are encoded by 9 genes, three each for the α1-, α2-, and β-adrenoceptors. Binding of a ligand to an adrenoceptor causes a change in conformation with subsequent activation of G proteins.
http://www.iuphar- db.org/GPCR/ChapterMenuForward?chapterID=1274

Adrenocorticotrophin (ACTH):
also known as adrenocorticotrophic hormone and corticotropin, a polypeptide hormone secreted by the adenohypophysis which is part of the pituitary gland. It stimulates the secretion of glucocorticoids and androgens from the zona fasiculata and zona reticularis of the adrenal cortex in response to corticotrophin releasing hormone.

Adrenolytic: a compound that abolishes the effects of catecholamines which are secreted by the adrenal medulla, ie it abolishes the effects of adrenaline and noradrenaline.

Adrenomedullin: a 52 amino acid peptide hormone discovered in 1993 and originally isolated from phaeochromocytomas of the adrenal medulla although it is present in many other tissues. There are several active fragments of adrenomedullin and they are all active vasodilators and hypotensives. This peptide has powerful vasodilator actions and it is thought that from studies in adrenomedullin gene-deleted mice that adrenomedullin plays an important role in vascular development. This peptide shown 27% homology with calcitonin gene-related peptide.

Adrenorphin: the first C-terminally amidated form of an opioid peptide isolated from human phaeochromocytoma tumors and thought to originate from proenkephalin A.

Adrenoreceptors: another name for adrenoceptors.

Adriamycin: the trade name of doxorubicin, an anthracycline, cytotoxic anticancer compound.

Adulticide: a pesticide which kills adult or mature insects. These compounds are particularly targeted at mosquitoes and heartworm and are commonly used in veterinary pharmacology. Examples include thiacetarsamide and melarsomine (both trivalent arsenic compounds) which function by binding to the sulphydryl groups of cysteine thereby denaturing insect proteins and enzymes.

Adverse drug reaction (ADR) : unpleasant, harmful, unwanted and sometimes fatal effects of a drug taken for the treatment of a specific disorder. In many countries physicians are required to report the occurrence of ADRs to committees which oversee drug safety such as the Committee on Safety of Medicines (which is part of the Medicines Control Agency) in the UK and the FDA in the US.

Ae : a symbol used in pharmacokinetics to denote the cumulative amount of drug excreted unchanged in the urine usually expressed in mg or μmole.

Ae : a symbol used in pharmacokinetics to denote the cumulative amount of drug excreted unchanged in the urine after a single dose and to time infinity usually expressed in mg or µmole.

Ael(m) : a symbol used in pharmacokinetics to denote the amount of metabolite eliminated usually expressed in mg or μmole.

Aequorin: a photoprotein obtained from a jellyfish of the genus Aequora. It binds irreversibly with Ca2+ ions and produces light in the visible spectrum when irradiated - the amount of emitted light is proportional to the Ca2+ concentration which can be measured. Aequorin is used for the measurement of Ca2+ levels both intra- and extracellularly.

Aer,ss: a symbol used in pharmacokinetics to denote the cumulative amount of drug excreted unchanged in the urine during a dosing individual and at steady state usually expressed in mg or μmole.

AF11377: a 15 amino acid peptide and cytokine receptor agonist.

AF64A: ethylcholine aziridinium

AF-DX-116: a selective M2 muscarinic receptor antagonist.
Hammer R et al. Binding profile of a novel cardioselective muscarinic receptor antagonist, AF-DX-116, to membranes of peripheral tissue and brain in the rat. Life Sci (1986) 38; 1653

AF-DX- 384: a non-subtype selective muscarinic receptor antagonist ((a)-5,11-dihydro-11-([(2-[2-[(dipropylamino)methyl]-1-piperidinyl)ethyl)amino] carbonyl)-6H-pyrido[2,3-b](1,4)benzodiazepine-6-one).

Affective disorder: a behavioural disorder characterized by changes in mood and which includes depression and mania. Depression is the most common affective disorder and ranges from mild and almost imperceptible mood changes to severe depression which may be accompanied by hallucinations and delusions.

Afferent nerves: neurones which conducts impulses towards the CNS. The opposite in efferent.

Affinity: a measure of the ease with which a drug will form a drug-receptor complex or a substrate will bind to an enzyme. Generally speaking, there is a 1:1 ratio between drug and receptor and at equilibrium the number of receptors occupied by a drug at a specific drug concentration depends on their affinity for that receptor. Affinity is the reciprocal of the dissociation constant. It is often expressed as the Kivalue.

Affinity assays: also known as binding assays.

Affinity labeling: a method of identifying or quantifying receptors by covalently binding a high affinity ligand such as a photoaffinity or a radiolabel to the receptor.

Aflatoxins: a family of mycotoxin alkaloids synthesized as secondary metabolites by the fungi Aspergillus flavus and Aspergillus parasiticus which commonly infest stored crops such as nuts. Aflatoxins are carcinogenic, teratogenic and hepatotoxic. They remain a threat to the welfare of livestock which are fed with contaminated feed. The most important of these mycotoxins is aflatoxin B1 which is converted to its epoxide in vivo by the action of cytochrome P450-dependent mixed function mono-oxygenases mainly in the liver where it is closely associated with the occurrence of hepatocellular carcinoma. This epoxide is highly reactive and reacts with many cellular macromolecules including DNA, RNA and proteins.

Agatoxins: a group of neurotoxins from the American funnel web spider (Agalenopsis aperta) comprising two distinct types, μ-toxins are relatively cysteine-rich proteins comprising 36-38 amino acids which act on insect although not on vertebrate voltage-sensitive sodium channels and function as sodium channel agonists. The ω-agatoxins are more diverse with higher molecular weights of 5-9kDa and act on various calcium channels where they acts as calcium channel blockers mostly in neuronal cells and blocking release of neurotransmitters. Agatoxins are used as pharmacological tools to study neuronal ion channels.
Olivera BM et al.
Calcium channel diversity and neurotransmitter release: The omega-conotoxins and omega-agatoxins. Ann Rev Biochem (1994) 63; 823-867

AGE: advanced glycation end products.

Aggrecanase: a protease thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 is a disintegrin and metalloproteinase and a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. Aggrecanase inhibitors are being developed as anti-inflammatories.

Agitoxins: a family of three closely-related scorpion toxins AgTX1, AgTX2 and AgTX3 used to investigate potassium channels.

Aglycone: also known as genin, the non-carbohydrate part of a glycoside.

Agmatine : a neurotoxic arginine metabolite which is produced in the bovine brain and which has clonidine-displacing substance activity. It is used as a ligand for the study if imidazoline receptor binding sites.
Li et al. Agmatine: an endogenous clonidine-displacing substance in the brain. Science (1994) 263; 966

Agonist: a chemical substance such as a neurotransmitter, hormone or drug which interacts with a receptor to give rise to a biological response in the effector cell. Agonists are divided into types according to the magnitude of the response they produce and the manner in which they produce it.
- A full agonist is one which will produce a maximal response in the effector tissue regardless of the number of receptor occupied. Receptor which are unoccupied at maximal effector response are spare receptors.
- A partial agonist is one which produces a sub-maximal response when it occupies all available receptors. A partial agonist will act as a competitive antagonist when a full agonist is present as it will occupy the sites to which the full agonist will attach. An example is the β-blocker oxprenolol which is used as a β1 blocker to treat hypertension, angina and arrhythmias. It does, however, have intrinsic sympathomimetic activity and is a partial agonist and can stimulate as well as block β receptors particularly where there is low sympathetic tone, ie it can mimic the action of sympathetic nerve stimulation.
- An inverse agonist (also known as a reverse agonist and negative agonists) is one which produces effects which are opposite to those of conventional (or classical) agonists but which act at the same receptor, ie reduces receptor activity. An example of this is where a conventional agonist lowers blood pressure but an inverse agonist raises it. One explanation of this effect is the assumption that the receptor exists in two forms or states, ie active and inactive forms (two-state theory). Conventional agonists have higher affinity for the active state of the receptor and the active receptor-ligand complex produces a high efficacy response. The inverse agonist binds preferentially to the inactive state of the receptor producing what is termed negative efficacy.
- A captive agonist is one which persistently binds to and activates a receptor despite extensive washout. Its effects can be inhibited by antagonist but once the antagonist is removed the agonist actions reappear.

Agonist gating: the change in conformation of a receptor caused by the binding of an agonist to it. The consequence of this conformation change is usually to allow ions to flow through the channel. An example is the nicotinic receptor. Channel opening occurs when 2 ACh molecules bind simultaneously to the 2 a subunits of the membrane-bound channel. This channel closes when one ACh molecule dissociates away. The mean channel lifetime is thus a function of mean time for which agonist stays bound.

Agonist- trafficking theory: the idea that different agonists either induce or stabilize different active receptor conformations. Classically, receptor theory indicated that only two receptor states, active and inactive, can exist and agonists bind and stabilize the active  state thereby increasing intracellular signaling. The agonist-trafficking theory suggest that different agonists stabilize different receptor active states and in turn this would selectively stimulate different signaling pathways.
Kenakin T. Agonist-receptor efficacy. II. Agonist trafficking of receptor signals. Trends Pharmacol Sci (1995) 16: 232-238

Agonist-induced endocytosis: a process in which a cell membrane receptor undergoes internalization to within the cell following binding of a ligand to it. Examples include receptors to transferrin, mannose-6-phosphate and low-density lipoprotein.
There are several mechanism responsible for receptor internalization such as clathrin-mediated endocytosis which is the most prominent and most studies mechanism. It is an efficient and rapid process in which clathrin forms a polymeric coating around the receptor to produce an endocytic vesicle. Other mechanisms involve non-clathrin processes such as the formation of cholesterol-rich caveolae, lipid rafts and Following internalization, the agonist-receptor complex is trafficked by endosomes after removal of the clathrin coating and the receptor protein is recycled to the cell membrane. Examples of receptors known to undergo agonist-induced endocytosis are the human chemokine receptors CCR5 and CXCR4 and muscarinic receptors. One consequence of this process is receptor desensitization.

Ahlquist, Raymond P: (1914-1983) American physiologist who compared the effects and relative potencies of a number of sympathomimetics including noradrenaline, adrenaline and isoprenaline on a number of different tissues. He observed that the order of potency differed as did the tissue response, ie contraction or relaxation. He thus proposed that these actions were mediated by two different receptors which he called α-receptors and β-receptors. A theory largely ignored a the time but taken up later by Black in his quest for β-selective adrenoceptor blockers.
Ahlquist RP. A study of adrenotropic receptors. Am J Physiol (1948) 153; 586-600

Air blast-induced seizure: a type of seizure.

Air pouch: an animal model used to investigate the anti-inflammatory properties of a test compound. Typically, mice (25-30g) are anaesthetized with ethyl ether and 10ml sterile air is injected into the subcutaneous tissue of the back. Three days later, these air pouches are re-inflated with 5ml sterile air. After 6 days, the air pouches are injected with saline (saline group), zymosan and vehicle (control group) or zymosan and test compound. Four hours after test compound administration, animals are killed and the exudate in the pouch collected. The cells, in the pouch exudate can then be counted as a measure of the anti-inflammatory effects of the test compound.
Edwards JCW, Sedgwick AD and Willoughby DA. The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. J Pathol (1981) 134; 147-156

Ajmaline: a rauwolfia alkaloid which has been used to normalize heart rhythm and to reduce blood pressure. At high dose in exhibits a tranquilizing effect. It can be obtained from Rauwolfia serpentine. The rauwolfia plant grown in India, Pakistan and similar areas and used as a febrifuge by Hindus.

AKR mouse: a strain of mouse first developed in 1956 which shows virtually 100% incidence of leukemia and used to investigate this blood disorder.

Alaptide: a cyclic peptide (8-methyl-6,9-diazaspiro[4.5]decane-7,10-dione) and melanostatin analogue which improves memory and suppresses amnesia in various animals probably by a dopaminergic mechanism.

Albomycin: a cyclic polypeptide sideromycin-type antibiotic produced by Actinomyces subtropicus. It is effective against gram-positive and gram-negative bacteria and acts by interfering with iron metabolism.

Aldo-ketose superfamily : a group of enzymes comprising alcohol dehydrogenase (EC and aldehyde reductase (EC They are monomeric NADPH-dependent oxidoreductases with wide substrate specificities for carbonyl compounds. Both enzymes play a role in the development of diabetic complications by catalysing the reduction of glucose to sorbitol which is oculotoxic and neurotoxic.
KM Bohren et al. The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. J Biol Chem (1989) 264; 9547-9551

Aldose reductase: an enzyme (EC officially known as aldehyde reductase which belongs to the aldo-ketose superfamily. It is present in many parts of the body such as the lens of the eye where it catalyzes the formation of polyhydric alcohols including sorbitol from glucose in the polyol pathway. When the supply of glucose in the eye is excessive as in poorly controlled blood sugar levels seen in diabetes, it enters the polyol pathway where it is converted to sorbitol. Sorbitol is osmotically active it can draw water into lens cells by osmosis causing the loss of transparency of these cells and even rupture. Sorbitol is a cause of diabetic retinopathy.

Aldose reductase inhibitors: compounds which inhibit the actions of aldose reductase and decrease the production of sorbitol. They are of interest because they can prevent eye and nerve damage in diabetics. Aldose reductase inhibitors are being developed to treat diabetic retinopathy.

Aldosterone: a potent mineralocorticoid (ie a corticosteroid involved primarily in sodium and potassium ion balance and also in the regulation of bodily water) secreted by the adrenal cortex which regulated sodium chloride resorption and potassium ion excretion by the kidney. Aldosterone secretion is controlled by blood levels of potassium ions and angiotensin II.

Aldosterone antagonist: compounds which antagonize the actions of aldosterone and so increase the secretion of sodium and chloride ions by the distal tubule of the kidney although potassium ion secretion is suppressed (hence the alternative name of potassium-sparing diuretic). An example is spironolactone which is used clinically to treat oedema, malignant ascites, nephritic syndrome, congestive heart failure and primary hyperaldosteronism.

Alfentanil: an opiate with rapid onset of anaesthetic action of between 1 to 2 minutes. It is used clinically as an opioid analgesic to induce intra-operative analgesia and as an analgesic in outpatient surgery.

Algogen: a substance that causes pain.

Alkaline phosphatase: an enzyme (EC which hydrolyses phosphate monoesters. Increases in the level of this enzyme is indicative of bone diseases such as Paget's disease or bone tumours.

Alkaloids: members of a class of highly diverse organic compounds comprised primarily of heterocyclic and fused heterocyclic compounds the majority of which are naturally occurring. They are often found in dicotyledonous plants and are important in phytochemistry and phytopharmacology. Many have potent pharmacological activity and many are highly toxic. Important examples in pharmacology include the tropane alkaloids which include cocaine. See http://en.wikipedia.org/wiki/Alkaloid

Alkalosis: also known as alkalaemia, an increase in the alkalinity of blood from the usual 7.35 or so to 7.8 or higher. It is caused by respiratory alkalosis, metabolic alkalosis or the effects of drugs. Examples include aspirin which uncouples oxidative phosphorylation mainly in the skeletal muscle leading to an increase in the production of CO2 which causes hyperventilation leading to respiratory alkalosis. It can be corrected by the administration of ammonium chloride solution and amino acid chloride solution.

Alkylamines: one of three main classes of histamine (H1) antagonists which include pheniramine, brompheniramine, chlorpheniramine, dimetindene, tolpropamine and triprolidine. The alkylamine moiety is shown in blue in the diagram below.


Alkylating agents: compounds which alkylate DNA, ie which attach an alkyl group to it, leading to mispairing during DNA replication or to chromosome breaks because the modified DNA base cannot be read correctly. The alkylation reaction involves the formation of a highly reactive carbonium ion (CH3+) which then combines with electron-rich groups (such as OH and SH) in the bases in DNA. Alkylating agents are mostly bifunctional, ie they supply two alkyl groups and are used in the treatment of cancer and include cisplatin, nitrogen mustards such as cyclophosphamide and melphalan, busulphan and nitrosureas such as lomustine and carmustine.

All-or-none response: also known as all-or-nothing response or quantal response, a type of response by an animal or tissue to a stimulus where the outcome is unequivocal, ie it either happens of fails to happen (unlike a graded response), such as death, success in completion of a task such as running in a maze in a defined time and loss of righting reflex.

ALLN: N-acetyl-L-N-[1-formylpentyl]-L-leucainamide, a cysteine protease and a calpain 1 inhibitor which blocks the cell cycle at G1/S because it inhibits cyclin B degradation.

Allocentric place discrimination task: a method used to evaluate working memory separately from and simultaneously with motivation, motor and sensory ability. It is used to test the effects of drugs on working memory.
Kikusui T. et al. The allocentric place discrimination task is selectively and highly dependent on the central muscarinic system in rats. Pharmacology Biochemistry and Behavior (2000) 65(1):131-139

Allodynia test: a test usually to evaluate the effects of drugs on allodynia which is pain from a non-painful (or not normally painful) source. Allodynia is dysesthetic meaning it displays a slow summation of pain. Examples include the hot plate test.

Allopathy : a term used to describe 'conventional' or Western medicine, ie medical practice involving the diagnosis of disease and its treatment with drugs.

Allopurinol: an antigout compound (1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) originally produced in 1956 in the search for antimetabolite antineoplastic compounds and which decreases the production of uric acid by inhibiting xanthine oxidase in tissues such as cartilage, joints and tendons.

allopurinol pathway

Allopurinol is an analogue of hypoxanthine, a breakdown product of adenine, which itself comes from adenosine, and is converted to alloxanthine by xanthine oxidase. The pharmacological actions of allopurinol are mainly due to alloxanthine. Allopurinol is a non-competitive inhibitor of this oxidase and has a long half-life of 18 to 30 hrs. The metabolites of xanthine oxidase are the relatively insoluble urates and uric acid. The deposition of urates in joints particularly the toe joints leading to the extremely painful development of gout. Allopurinol is used in the prophylaxis and long-term treatment of gout and hyperuricemia.

allopurinol tautomer

Allosteric activator: a compound which binds to an allosteric or allotopic site on an enzyme or receptor and increases or enhances the action of the ligand binding to the recognition site.

Allosteric (allotopic) interaction: an interaction between ligands which bind to the same receptor site or to recognition sites on the receptor that overlap.

Allosteric (allotopic) modulator: a ligand which increases or decreases the action of an agonist or antagonist by binding to an allosteric or allotopic site on a receptor macromolecule.

Allosteric transition: a transition of receptor macromolecule between multiple conformational states.

Alloxan: a heterocyclic substance originally discovered by J. v. Leibig in mucus secreted during dysentery and one which is used to induce experimental diabetes (a diabetogenic) as it preferentially destroys β-cells of the islets of Langerhans in the pancreas. Alloxan and its reduction product, dialuric acid, form a redox cycle which generate superoxide radicals in pancreas cells. These radicals undergo dismutation to form hydrogen peroxide and highly reactive hydroxyl radicals are formed from this by the Fenton reaction. The action of reactive oxygen species together with a massive increase in cytosolic calcium concentration causes rapid destruction of β-cells and hence a marked fall in insulin output.

Alloxan diabetes: an animal model of diabetes mellitus in which alloxan is used to destroy pancreatic islet cells and so produce the manifestations of diabetes.

Allylamines: a class of antifungal compounds which inhibit ergosterol biosynthesis by inhibiting squalene epoxidase so the fungal cell cannot produce membrane sterols. This makes the membrane permeable leading to cell death. Examples include terbinafine (used to treat athlete's foot) and naftifine. The allylamine moiety is shown in blue.


Alteplase: also known as rt-PA and tissue-type plasminogen activator, a recombinant 527 amino acid single chain protein and fibrinolytic. It activates plasminogen to form plasmin which degrades fibrin so breaking up thrombi. It is used clinically in acute myocardial infarction and pulmonary embolism.

A (m): a symbol used in pharmacokinetics to denote the amount of metabolite in the body usually expressed in mg or μmole.

Am80: a synthetic retinobenzoic acid and all-trans retinoic acid agonist more potent than this compound at inducing the differentiation of acute promyelocytic leukemia. Am80 binds to two of the three RAR subtypes (RAR α and β).

Amantadine: an antiviral and antiparkinsonian agent used to treat Parkinson's disease, influenza and hepatitis. It appears to release dopamine from dopaminergic nerve terminals in the brain although the exact mechanism is not clear.

Amaryllidaceae alkaloids: a class of alkaloids obtained from the plant family Amaryllidacea. They comprise phenylisoquinolide alkaloids and include galantamine which is used clinically as an anticholinesterase.

Amatoxins: a group of bicyclic octapeptides which are toxic components of the death cap fungus Amanita phalloides. These toxins inhibit nucleoplasmic RNA polymerase II in eukaryotic cells which causes necrosis of the liver and kidneys. The vast majority of cases of fatal mushroom poisoning are due to ingestion of Amanita phalloides or related species.

Ambenonium: a rapidly reversible inhibitor of acetylchloinesterase used as a pharmacological tool to investigate role of acetylcholinesterases.
Hodge AS et al. Ambenonium is a rapidly reversible noncovalent inhibitor of acetylcholinesterase, with one of the highest known affinities. Mol Pharmacol (1992) 41; 937-42

Ambulometer: a device to measure ambulation, ie free walking movement. Occasionally used in experimental animals to measure hyperactivity such as that induced by morphine.

Amdrup pouch: a form of modified Pavlov pouch.
Shibata C, Sasaki I, Naito H, Matsuno S. Modified procedure with a surgical stapler for construction of a Pavlov pouch in dogs. Lab Anim Sci (1996) 46(4); 438-441

Ames test: a test of the mutagenic effects of compounds which is used as an indicator of their carcinogenicity. This test was developed by Bruce Ames in the US. This in vitro test uses mutant strains of Salmonella typhimurium or other bacteria which cannot grow in the absence of histidine because of defects in their synthesis of histidine carboxylase. Mutagens (also presumed to be carcinogens) can elicit changes in these bacteria allowing them to regain their ability to grow in histidine-deficient medium. The Ames test can also be carried out by firstly treating the suspected mutagen/carcinogen with the S9 fraction of rat liver (so named as it is the supernatant of liver homogenate after centrifugation at 9000g) to facilitate the metabolic generation of mutagen/carcinogen from promutagen/procarcinogen. There is a very high correlation between bacterial mutagenicity of compounds and their carcinogenicity and this test is routinely used in the very early stages of drug development when the toxicity profile of new chemical entities is being assessed.

Amethocaine: also known as tetracaine, a local anaesthetic used as a 4% gel for topical induction of anaesthesia prior to venepuncture or venous cannulation.

Amicetins: a group of pyrimidine (nucleoside) antibiotics synthesized by various Streptomyces spp. and having actions against some gram-positive bacteria.

Amikacin: an aminoglycoside antibiotic and a kanamycin derivative used clinically in the treatment of serious gram-negative infections which are resistant to gentamicin such as seen in septicaemia, neonatal sepsis, meningitis, biliary tract infection, acute pyelonephritis and endocarditis.

Amiloride: a potassium-sparing diuretic which inhibits sodium resorption and decreases potassium excretion by the collecting tubules and ducts of the kidney. It blocks luminal sodium channels. Amiloride is a weak diuretic, it causes retention of potassium and is used clinically to treat oedema.

Amin: a symbol used in pharmacokinetics to denote the minimum amount of drug in the body necessary to elicit a particular level of response usually expressed in mg or μmole.

Amine-depleting drug: compounds which can deplete nerve terminals of amino neurotransmitters. Examples include reserpine.

Amino acid transporters : specialized transporter mechanisms which work in parallel with peptide transporters and transport amino acids across cell membranes to fulfill the metabolic requirements of cells.

Aminoalkylethers: a class of antihistamines and anti-inflammatory compounds which include diphenhydramine, doxylamine and medrylamine. The aminoalkylether moiety is shown in blue.


Aminoarylcarboxylic acid derivatives<: a class of non-steroidal anti-inflammatory drugs (NSAIDs). Examples include flufenamic acid, tolfenamic acid and mefanamic acid.

4-Aminobutyric acid (GABA): also known as γ-aminobutyric acid and 4-Abu, a non-protogenic amino acid produced from L-glutamate by the action of glutamate decarboxylase.

Aminocaproic acid: a fibrinolysis inhibitor used to enhance coagulation in cases of continued bleeding. See http://www.rxlist.com/cgi/generic/amicarpre_cp.htm

Aminocyclitols: a class of antibiotics similar to the aminoglycosides and produced by Streptomyces sp particularly Streptomyces spectabilis and Streptomyces tenebarius. Examples include spectinomycin and apramycin which are used in veterinary pharmacology to treat gram-negative aerobe and Mycoplasma infections such as those causing airsaculitis and chronic respiratory disease in turkey poults and porcine coliobacillosis caused by susceptible strains of E. coli. Aminocyclitols bind to the 30S ribosome subunit and inhibit protein synthesis.

N-(2-Aminoethyl)-N-n-hexyl-5-isoquinoline sulphonamide: a vasodilator which is as potent as diltiazem in vivo.

Aminoglutethimide: a non-steroidal aromatase inhibitor which inhibits the conversion of androgens to oestrogens in peripheral tissues. It is used clinically to treat advanced breast or prostate cancer as well as Cushing syndrome due to malignant disease but newer aromatase inhibitors are preferred as they are better tolerated.

Aminoglycosides: a class of antibiotics having complex chemical structures and which inhibit bacterial cell wall synthesis. Examples include streptomycin, amikacin, tobramycin, gentamicin, neomycin and framycetin. Aminoglycosides are bactericidal are used clinically to treat both gram-positive and gram-negative infections, Streptomycin is active against Mycobacterium tuberculosis. Bacterial resistance to aminoglycosides can limit their use.

Aminoguanidine: also known as guanylhydrazine, an inhibitor of the formation of advanced glycation end products (AGE) and used clinically in the treatment of diabetic complications such as nephropathy.

p-Aminohippurate (4-aminohippurate): a compound used to measure kidney function. It is excreted by the organic ion transport system of the renal tubules and its renal clearance is taken as a measure of secretory function of the nephron. The measurement of the renal extraction of this compound can be used in the measurement of renal blood flow.

Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA): a selective inotropic glutamate receptor agonist used in the classification of excitatory amino acids receptors. In many central nervous system synapses AMPA receptors (also known as quisqualate receptors) mediate fast excitatory transmission.
Krogsgaard-Larsen P et al. New class of glutamate agonists structurally related to ibotenic acid. Nature (1980) 284; 64

6-Aminonicotinamide: a protein synthesis inhibitor and a vitamin antagonist with teratogenic effects.

Aminopeptidases: a class of over a dozen exopeptidase which cleave peptide bonds near the N-terminal of polypeptides. They are largely zinc-metalloenzymes containing highly-conserved zinc-binding motifs and are distributed in a wide range of tissues. Several aminopeptidases are of interest in pharmacology as they are the targets for enzyme inhibitors.
- Aminopeptidase N (officially known as membrane alanine aminopeptidase, (EC, also known as alanine aminopeptidase, preferentially hydrolyses polypeptides with a N-terminal alanine. including Met-Lys-bradykinin, Lys-bradykinin and (Leu5)-enkephalin. This enzyme is present in a large number of tissues but exhibits high activity in the brush border membranes of proximal tubules in the kidney and intestines.

Aminopeptidase inhibitors: compounds which inhibit aminopeptidases and which have useful pharmacological actions, ie aminopeptidase B inhibitors and aminopeptidase N inhibitors. Examples of these inhibitors include bestatin and amastatin which are non-selective for isozymes and have immunomodulating and anti-metastatic actions.

Aminophylline: a stable mixture or combination of theophylline and ethylenediamine used clinically to treat reversible airway obstruction and acute severe asthma as it acts as a bronchodilator.

Aminopterin: an anticancer, rodenticide mutagenic compound and folic acid antagonist. It has been used as an abortifacient. It is N-[4-[(2,4-diamino-6-pteridylmethyl)amino]benzoyl]glutamic acid.

4-Aminopyridine: a potassium channel antagonist and an enhancer of ACh release.

4-Aminoquinolines: a class of antimalarial agent which includes amodiaquin and chloroquine. The structure of chloroquine is shown below with the 4-aminoquinoline moiety shown in blue.


8-Aminoquinolines: a class of antimalarial agent which includes primaquine. The structure of primaquine is shown below with the 8-aminoquinoline moiety shown in blue.


Aminosteroids: a class of non-depolarizing muscle relaxants which include pancuronium, rocuronium and vecuronium. They are competitive antagonists of neuromuscular nicotinic receptors.


Amiodarone: a benzofuran derivative and Class III antiarrhythmic agent which has been use to treat ventricular arrhythmias.

Amitriptyline: a tricyclic antidepressant and an atypical antipsychotic used clinically to treat depressive illness and nocturnal enuresis in children. It blocks the uptake of amines into nerve terminals by competing for the binding site of the amine carrier protein.

Amlodipine: also known as UK-48340, a dihydropyridine-type calcium antagonist (2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridine dicarboxylic acid 3-ethyl 5-methyl ester) used in the treatment of angina and hypertension. It is an antagonist of L-type calcium channels and acts by binding to the á1 subunit of the cardiac calcium channel.

Amnestic syndrome: loss of memory with the exception of short-term memory.

Amnion: see chick amnion

Amoebicides (amebicides): also known as antiamoebics, agents which kill amoeba, unicellular organisms typified by Entameba histolytica which can cause potentially fatal infectious disease in humans such as amoebic dysentery, pulmonary amoebiasis and cutaneous amoebiasis. The most common treatment of pathogenic strains is diloxanide furoate and metronidazole and other 5-nitroimidazole compounds including orindazole are indicated for the treatment of symptomatic intestinal infections. Other drugs include tindazole. Metronidazole is used to treat amoebiasis in small animals.
Di Perri G, Strosselli M, Rondanelli EG. Therapy of entamoebiasis. J Chemother (1989) 1(2); 113-122

Amoxycillin (amoxicillin): a semisynthetic, broad-spectrum, orally available antibacterial [2S-[2,5,6(S*)]]-6-[[amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid) which is structurally related to penicillin. Amoxicillin is used clinically against gram-positive and gram-negative infections and in the prophylaxis of endocarditis. Amoxicillin is acid-stable but β-lactamase sensitive and so may be co-administered in a formulation with clavulanic acid (a β-lactamase inhibitor).

AMPA: amino-3- hydroxy-5-methyl-4-isoxazole propionic acid

AMPA-type glutamate receptor: a type of glutamate receptor.

Ampakines: a group of small benzamide compounds developed for the improvement of cognition which act by binding to the accessory site of AMPA-type glutamate receptors and allosterically produce positive modulation to improve performance in a variety of behavioural tasks. Examples include CX516 and CX509 (1-(1,3-benzodioxol-5-ylcarbonyl)-1,2,3,6-tetrahydropyridine).

Amphenicols: a group of broad-spectrum antibiotics including chloramphenicol (obtained from Streptomyces venezuelae), thiamphenicol and florfenicol. Chloramphenicol is a potent broad-spectrum antibiotic used clinically to treat life threatening infections such as those caused by Haemophilus influenzae and for typhoid fever. Thiamphenicol and florfenicol have been used in veterinary pharmacology to treat fowl cholera and bovine respiratory disease as well as furuncolosis in Atlantic salmon, pseudotubercullosis in yellowtail and vibriosis in goldfish.

Amphetamines: an class of compounds containing a 1-phenyl-2-aminopropane skeleton which has sympathomimetic activity throughout the central and peripheral nervous system. In experimental animals amphetamine causes increased alertness, increased locomotor activity, increase grooming and increased aggression, ie it is a psychomotor stimulant and is used a s drug of abuse.
Amphetamines have slang terms in various parts of the world of A, ace, amph, amphets, billy whiz, black rock, blackbirds, blues, bombido, California sunshine, cartwheels, chalk, co-pilots, crystals, diet pills, dominoes, double cross, nuggets, oranges, pep pills, poor mans cocaine, powder, red devil, speed, splash, sulph, sweets, truck drivers, uppers, wake ups, whites, whiz, woodpeckers and zoom.

Amphetamine-induced stereotypy: behavioural conditions which can be induced in experimental animals by the administration of amphetamine. Symptoms include sleep or immobility, activity, sniffing over a wide area or sniffing over a restricted area of the cage, occasional biting or licking or continuous biting or licking and because most of these actions are repeated for no apparent reason it is referred to as stereotypy. These symptoms become more pronounced with increasing dose. Amphetamine-induced stereotypy is used as an animal model of schizophrenia. Amphetamine is known to cause release of large amounts of dopamine in the brain and anti-schizophrenic drugs which antagonize dopamine reduce or abolish this stereotypic behaviour.

Amphibian toxins: a group of toxins which are produced by toads, salamanders, frogs, and newts. They are markedly heterogeneous, ie they have widely different chemical structures and include batrachotoxins and tarichatoxins. They are generally toxic to cardiac muscle and inhibit neurotransmission.

Amphipathic: a compound with both hydrophilic and hydrophobic regions. Examples include surfactants.

Amphotericin: a macrolide polyene antibiotic which binds to fungal cell membranes to affect permeability and impair transport functions. After binding to fungi and some protozoa but not to bacteria, it forms a pore in the cell membrane leading to a loss of intracellular K+. It binds to ergosterol, a major constituent of fungal cell walls. It is used clinically in the treatment of systemic candidiasis, cryptococcosis and histoplasmosis often in combination with other antifungals.

Amscarine: an anticancer drug which binds to DNA to inhibit both RNA and DNA synthesis and which inhibits topoisomerase II. It has a similar pharmacological and toxicological profile to doxorubicin and is used clinically to treat acute myeloid leukaemia.

Amygdaloid body: a round mass of grey matter in the temporal lobe in front of the inferior horn of the lateral ventricle. Neurones run to it from the olfactory (smell) organs and to the hypothalamus and mediodorsal nucleus of the thalamus. It comprises the basolateral and corticomedial nuclei.

Amygdaloid kindling: a method of kindling used to induce seizures by stimulation of the amygdaloid body and used in animal models to study epilepsy. It is caused by repeated application of weak electrical stimulation to the amygdaloid body at intervals which results in the progressive development of generalized convulsive seizures. Typically, under pentobarbital anaesthesia rats or cats are fixed to a stereotaxic apparatus and bipolar electrodes are implanted into the right amygdala. These electrodes are fixed with cement and animals are allowed to recover. Low intensity stimulation of the amygdala is applied bipolarly every day at until a generalized convulsion is obtained. Alternatively, seizures can be induced by repeated daily intra-amygdaloid microinjections of about 2nmol N-methyl-D-aspartate.

Amygdalin: a bitter-tasting cyanogenic glycoside ([(6-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy]benzeneacetonitrile) present in bitter almonds and in peach and apricot pits and considered to be an active component of laetrile. Its cytotoxic effects are due to the production of cyanide.

Amyl nitrate: an organic nitrate and vasodilator which is used in the treatment of angina.

Amylin: also known as islet amyloid polypeptide, a naturally occurring 37 amino acid peptide hormone co-secreted with insulin from the β-cells of the pancreas following the intake of food. Amylin appears to decrease food intake through both central and peripheral mechanisms and indirectly does so by slowing gastric emptying. It was first identified in 1987 and observed to be deficient in type 1 diabetics and in some type 2 diabetics. Amylin acts as a satiety agent, ie a substance that signals to the body that its hunger has been fulfilled, and its replacement may improve the control of blood sugar levels in diabetes mellitus. Human amylin, however, shows physicochemical properties predisposing it to form aggregates and amyloid fibres (which may cause neurodegenerative diseases) which makes it unsuitable for direct pharmacological application. Amylin receptor agonists are being developed to overcome this problem.

Amylin receptors: receptors to which amylin binds to illicit its anorectic actions.
Poyner DR et al. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacological Reviews (2002) 54(2); 233-46
Young A. Receptor pharmacology. Adv Pharmacol (2005) 52:47-65

Amylin receptor agonists: compounds which mimic the effects of amylin at its receptor sites, ie compounds which suppresses glucagon secretion and reduce weight. They are being developed as agents to control body weight as they have actions and pharmacokinetic and pharmacodynamic properties similar to the native peptide. They include the stable amylin analogue, pramlintide.
Reda TK et al. Amylin, food intake, and obesity. Obes Res (2002) 10(10):1087-91

Amylin receptor antagonist: compounds which block the response caused by amylin at its receptor sites. Although amylin is important in blood glucose control, it is deposited in large amounts in the brains of Alzheimer's patients where it causes hippocampal and cortical disorders. and provides a novel therapeutic approach for Alzheimer's disease. Amylin is thought to modulate ion channels in the cholinergic neurones in the basal forebrain. Amylin receptor antagonists are being developed in the search for treatments to neurodegenerative disease.

AN,max: a symbol used in pharmacokinetics to denote the maximum amount of drug in the body after the Nth dose having a fixed size and dosing interval has been administered and shown in mg or μmole.

AN,min: a symbol used in pharmacokinetics to denote the minimum amount of drug in the body after the Nth dose having a fixed size and dosing interval has been administered and shown in mg or μmole.

AN,t: a symbol used in pharmacokinetics to denote the amount of drug in the body after the Nth dose and at time t shown in mg or μmole.

Anabolism: the effects of metabolic reactions which synthesize molecules.

Anaesthetic (anesthetic): a substance which renders an area or region of the body insensitive to pain (local anaesthetic) or which renders a patient or animal unconscious, hyporeflexic and insensitive to pain (general anaesthetic). Anaesthetics are used in surgery and dentistry routinely to prevent pain when invasive procedures are carried out.
- Local anaesthetics act by inhibiting propagation of nerve impulses by decreasing the rate and degree of depolarization of nerve cells. They inhibit sodium channels in the nerve thereby decreasing membrane permeability to sodium ions. Examples include lidocaine, procaine, bupivicaine and mepivicaine and are given by injection (for peripheral nerve block, spinal anaesthesia and neurolytic anaesthesia) or by topical application (for infiltrative anaesthesia described below).
- General anaesthetics may be injectable such the barbiturates (examples include pentobarbital, methohexital and thiopental) and ketamine or inhalation anaesthetics such as halothane, methoxyflurane and enflurane. These act according to the lipid theory (where they interact with a lipid bilayer to modulate membrane function) or according to the protein theory (where they bind to discrete hydrophobic domains on protein molecules particularly those in ion channels).
- Regional or infiltration anaesthetics are used largely in dentistry to anaesthetise a specific local area such for a surgical procedure such as a tooth extraction. Examples of infiltration anaesthetics include lidocaine.

Analeptic: an old term used to denote a group of drugs that had restorative effects on the CNS and which inhibited the effects of depressants such as anaesthetics, ethanol and hypnotics. Examples of analeptics include caffeine, picrotoxin (once used to promote respiration in cases of barbiturate poisoning), oxygen and doxapram.

Analgesics: also referred to as painkillers, compounds which dull the sense of pain but, unlike anaesthetics, do not cause loss of consciousness. Analgesics are classified as non-opioid (non-narcotic) and opioid (narcotic) analgesics.
- Non-opioid analgesics include aspirin and other NSAIDS and tend to be used for musculoskeletal pain, headache and dysmenorrhoea, whereas opioid analgesics are more suitable for visceral pain such as that experienced in terminal illnesses.
- Opioid analgesics include morphine and act via opioid receptors in the brain to produce euphoria and mental detachment.

Analysis of variance (ANOVAR) : a statistical test used to test the significance of the mean difference between groups.

Anandamide: an arachidonoylethanolamide and a naturally occurring derivative of arachidonic acid which activates cannabinoid receptors in the brain.
Vogel et al. Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. J Neurochem (1993) 61; 352

Anandamide transport inhibitors: compounds which inhibit uptake of anandamide by neurones. Examples include AM404 (N-(4-hydroxyphenyl)-arachidonylamide), VDM 11 and olvanil. Anandamide transport inhibitors are being developed for potential use in the treatment of spasticity in disorders such as multiple sclerosis.

Anatoxin: a selective agonist of neuronal (α-bungarotoxin-sensitive) nicotinic cholinoceptors.

Anchimeric assistance: also known as neighbouring group participation, a term used in drug design and medicinal chemistry to show that a neighbouring atom or group influences a reaction which is occuring to an adjacent atom. It is due to a direct interaction between the reaction centre with a lone pair of electrons of an atom or with the electrons of a σ- or π-bond contained within the parent molecule but which are not conjugated with the reaction centre. Generally, this effect increases rates of reaction. An example is the hydrolysis of aceylcholine where the positively charged nitrogen atom has an electron-withdrawing effect leading to relatively easy hydrolysis.

Ancrod: a thrombin-like protease enzyme from the venom of the Malaysian pit viper (Agkistrodon rhodostoma) which has been used an anticoagulant.

Androgens: a group of male gonadal hormones (but which are also secreted by the ovaries of women) which include testosterone, androsterone and androstenolone. They are responsible for the development of male characteristics of individuals.

Angel dust: also known as phencyclidine.

Angiotensins: a family of small peptides which are formed from a tetradecapeptide terminal of a circulating a2 plasma globulin (angiotensinogen) by renin in various tissues especially the lungs. Angiotensins I, II, III and IV are known. They have various cardiovascular actions including vasoconstriction, an increase in blood pressure release of aldosterone from the adrenal cortex. Angiotensin I is converted to angiotensin II (a potent vasoconstrictor) by angiotensin converting enzyme. The name stems from alternative names for angiotensin II and was coined in 1958, ie angiotonin and hypertensin.

Angiotensin converting enzyme (ACE): also known as kininase II and officially as dipeptidyl-peptidase A, an enzyme (EC which converts the inactive decapeptide angiotensin I to the potent octapeptide vasoconstrictor angiotensin II in the renin-angiotensin system. ACE is found predominantly in the pulmonary capillaries.

Angiotensin converting enzyme inhibitor (ACEI): compounds which inhibit the production of the potent vasoconstrictor angiotensin II by inhibiting angiotensin converting enzyme and so lower blood pressure. Many ACEI are used clinically and include captopril (the first to be used), enalapril, lisinopril, cilazapril, fosinopril, perindopril, quinapril, ramipril and transolapril. ACEI prodrugs include enalaprilat (converted to enalapril) and ramiprilat (converted to ramipril).

Angiotensin receptors: a class of four G protein-coupled receptors sensitive to the actions of angiotensins. They include AT1, AT2, AT3 and AT4 receptors and they differ in tissue distribution and actions they mediate. For example, AT1 receptors are coupled to phospholipase C and binding of angiotensin II to this receptor increases cytosolic Ca2+ level via stimulation of this receptor. This receptor mediates a range of vascular actions including vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion and cardiac hypertrophy.
de Gasparo M et al. International Union of Pharmacology. XXIII. The Angiotensin II Receptors. Pharmacological Reviews (2000) 52(3); 415-472
See http://www.iuphar-db.org/GPCR/ChapterMenuForward? chapterID=1277

Angiotensin receptor agonists: compounds which stimulate angiotensin receptors. They are used a pharmacological tools to investigated angiotensin receptor subtypes. Examples include the non-peptide AT1 partial agonist L-163,491 and the AT2 receptor ligand CGP42112A.

Angiotensin receptor antagonist: also known as angiotensin receptor blockers (ARBs), compounds which block angiotensin receptors. The most important clinically are the AT1 receptors as theses mediate the vasopressor action of angiotensin II at this site and so lower blood pressure. Examples include the sartans, eg candesartan, erbesartan, losartan, olmesartan and valsartan.

Anhalonium alkaloids: isoquinoline alkaloids found mainly in cacti. They are often weak narcotic and paralyzing agents and examples include lophophorin, hordenine and mescaline.

Anhedonia: a lowered ability to experience pleasure which can be disorder-induced such as in schizophrenia or drug-induced such as experienced by abusers of cocaine.

Animal models: animals that have been genetically modified or whose physiology, anatomy and/or biochemistry has been altered by an exogenous compound or physical change so that they mirror in some way the physiological, biochemical and pathological processes involved in human disease. They are used to study a wide variety of disorders and new animal models are constantly being developed largely to more accurately simulated disease processes.

Animal models of infection: a disease state in an animal caused by an infective pathogen where the physiological and pathological processes involved mirror in some ways the disease in humans. There are many animal models of infection.
Handbook of Animal Models of Infection: Experimental Models in Antimicrobial Chemotherapy. Zak and Sande (Eds). Academic Press 1999

ANO: antisense oligonucleotides

Anococcygeus preparation: a smooth muscle preparation of the urogenital tract which runs on to form the retractor penis. Motor innervation is sympathetic with noradrenaline as transmitter although the relaxant parasympathetic transmitter is nitric oxide. This muscle preparation is used as a model of the mechanisms underlying nitrergic innervation. In rats it has been used to study the in vitro effects of drugs on α1-adrenoceptors and GABAB receptors.
Gibson A, McFadzean L. Biology of the anococcygeus muscle. Int Rev Cytol (2001) 205; 1-35. Review
Gillespie JS. The rat anococcygeus muscle and its response to nerve stimulation and to some drugs. Br J Pharmacol (1972) 45; 404-416

Anomer: a stereoisomer of a sugar which differs only in the way it is configured about its carbonyl (anomeric) carbon atom.

Anorectic: also referred to as anorexiant, anorexic and anorexigenic, a substance which suppresses appetite leading to a decrease in food intake and consequent weight loss.

Anorexiant: anorectic

Anorexigenic: anorectic

ANOVAR: analysis of variance

ANSA antibiotic: antibiotics (and anticancer drugs) which comprise the ansa backbone or an aliphatic bridge linking two nonadjacent atoms in a ring in their structure at the para or meta positions. This chain is commonly 10 to 12 carbon atoms long. Examples include rifamycin, napthomycin, halomicin, kendomycin and streptovaricin.

Ansamycins: a class of polyketide natural products which include rifamycin, ansamitocin, radicicol, herbimycin B, and geldanamycin. Ansamycin antibiotics inhibit the function of the hsp90 family of heat shock proteins causing selective degradation of intracellular proteins which regulate processes such as cell proliferation, cell cycle regulation, and prosurvival signalling cascades. Consequently, ansamycins display potent cell proliferation inhibiting and anticancer activity.

Antabuse: also known as disulfiram.

Antacid: a substance which neutralizes gastric acid. They can act non-systemically solely in the gut such as magnesium trisilicate or systemically where they alter the acid-base balance of the entire body such as sodium bicarbonate.

Antagonism: the effect of a drug where it neutralizes the response elicited by another drug or endogenous ligand usually at a receptor site. Antagonists can be divided into several types according to the mechanism and nature of the antagonism.
- Chemical antagonism is caused by the combination of an agonist with an antagonist where inactivation of the agonist is the result. An example of this is the interaction between dimercaprol and mercuric ions.
- Physiological antagonism, also known as functional antagonism, is caused by an agonist and an antagonist acting at two independent sites leading to independent and opposite effects rather than acting at the same receptor site.
- Pharmacological antagonism is caused by the action of an agonist and an antagonist at the same site which is usually a receptor. This is subdivided into irreversible antagonism, competitive antagonism, non-competitive antagonism, non-equilibrium antagonism, nonspecific antagonism, pseudo-irreversible antagonism, neutral antagonism and surmountable, unsurmountable (also known as insurmountable) and nondesensitizing antagonism.
- Irreversible antagonism is where the antagonist binds so strongly to the receptor that dissociation from the receptor is extremely slow and so it appears irreversible. This form of antagonism is not surmountable or very slowly surmountable with the addition of agonist. Examples include organophosphorus cholinesterases.
- Pseudoirreversible antagonism act like irreversible antagonist except that no covalant bond is formed between the antagoinst and receptor.
- Competitive antagonism is where the effects of the antagonist can be overcome with an increase in agonist concentration as they both compete for the same receptor site. In the presence of a fixed concentration of agonist, increasing concentrations of a competitive antagonist will gradually inhibit the response to the agonist. On a plot of the percentage of maximal response against the log of the agonist concentration, increasing concentrations of a competitive antagonist will shift the dose-response curve to the right.
- A non-equilibrium antagonist is one which forms a stable combination with specific receptors but which is not considered to be truly irreversible. It is qualitatively different from classical competitive antagonism because the agonist and antagonist are not in mass-action equilibrium with the receptors and the antagonism produced is referred to as non-equilibrium antagonism. Examples include the buprenorphine derivative, 18,19-dehydrobuprenorphine, which has potent and long-lasting antinociceptive effects.
- Non- desensitizing antagonism is where the antagonist does not induce a decrease in receptor sensitivity to ligand.
- Non-specific antagonists act as antagonists at several receptor subtypes.
- Neutral antagonism is where a compound reverses the effects an agonist or an inverse agonists but has no antagonistic effect by itself.
- Orthosteric antagonist is where the antagonist blocks the agonist from binding to the receptor by steric hindrance of the receptor binding site.
- Orthosteric insurmountable antagonists directly interact with the primary agonist binding site to prevent access for activating ligands.

Antamanide: a cyclic decapeptide obtained from the death cap fungus (Amanita phalloides). It binds alkali metal ions particularly sodium ions (more so than potassium ions), it readily forms complexes with Na+ and Ca2+ ions and, because of its lipophilicity, it acts as a sodium ionophore. It also has antiproliferative actions on tumour cells and immunosuppressant actions. Antamanide also acts as an antidote to phallotoxins and amatoxins.

Anterior tibialis-sciatic nerve preparation: also known as the sciatic nerve-tibialis anterior muscle preparation, a nerve-muscle preparation typically from the guinea pig, rat, cat or dog which can be used to investigate the properties of compounds on neuromuscular blockade in vivo.

Anterograde: moving forward.

Anterograde transneuronal degeneration: degeneration of a neurone following destruction of an afferent neurone.

Anthracyclines: a class of antibiotic compounds which are closely related to the tetracyclines. They are used clinically not as antibiotics but as anticancer agents because of their potent cytotoxicity. Examples include doxorubicin, idarubicin, epirubicin, mitozantrone, dactinomycin, mitomycin and the bleomycins. They act by binding to DNA and inhibit both DNA and RNA synthesis although other mechanisms are involved. Doxorubicin destabilizes the DNA-topoisomerase II complex and inhibiting DNA replication. Dactinomycin intercalates into the minor groove of DNA between adjacent guanosine and cytosine pairs inhibiting the movement of RNA polymerase along the DNA strand so inhibiting its actions. Mitomycin is enzymically activated in cells form a bifunctional alkylating agent which cross-links with DNA and may degrade it by forming free radicals.

Anthroposophic medicine: medicines and medical practice based on the teachings of the Austrian philosopher Rudolf Steiner (1861-1925).

Antiacne: compounds used to treat acne, an inflammatory disorder of skin follicles which can cause permanent scarring of the skin if untreated. Examples of antiacne compounds include topical application of benzoyl peroxide, azelaic acid, topical antibacterials including erythromycin and clindamycin, topical retinoid treatment such as that with isotretinoin and adapalene and corticosteroids.

Antiallergic: compounds used to treat allergies, inflammatory disorders of the skin and mucous membranes caused by hypersensitivity to allergens. Antiallergics comprise a variety of compounds including histamine receptor antagonists, immunosuppressants and inhibitors of the production and actions of inflammatory mediators.

Antialopecia: compounds used to treat alopecia, the absence or loss of hair and baldness. Male-pattern baldness can be treated with minoxidil.

Antiamoebic (antiamebic): also known as amoebicides.

Antianaemics (antianemics): compounds for the treatment of anaemia, a blood disorder in which the number of red blood cells per mm3 blood, the amount of haemoglobin per unit volume blood and/or the volume of packed red blood cells per volume of blood is lower than normal. There are various causes of anaemia and the treatment depend on the cause. Iron-deficiency anaemia is treated with oral iron in the form of an iron salt such as ferrous sulphate or ferrous fumarate. Megaloblastic anaemias such as pernicious anaemia and which are due to a lack of vitamin B12 or folate are treated with cyanocobalamin or hydroxycobalamin. Aplastic, hypoplastic, haemolytic and renal anaemias are treated with erythropoietin or corticosteroids.

Antiandrogens: compounds which inhibit the effects of androgens, naturally occurring hormones such as testosterone which is necessary for the function of accessory male sex organs and for the development of male sex characteristics. Excess androgen production causes hypersexuality and sexual deviation in the male. Antiandrogens include cyproterone acetate and the 5-reductase inhibitor finasteride.

Antianginal: compounds used to treat angina, severe and often constricting pain in and around the heart due to an insufficient oxygen supply to the myocardium due in turn to constriction of coronary blood vessels. Antianginal therapy comprises organic nitrates (ie glyceryl trinitrate), calcium channel blockers (ie verapamil, nifedipine and nicardipine) and potassium-channel openers (ie nicorandil). These cause coronary vasodilation thereby increasing the oxygen supply to myocardial tissue.

Antiangiogenesis therapy: a strategy of treating tumours with compounds that inhibit the formation of new blood vessels which are essential to tumour growth. This method of treatment starves the tumour of the nutrients it needs for its growth and can shrink tumours but withdrawal of treatment usually results in their regrowth.

Antianxiety drug: also known as anxiolytics.

Antiaromatases: also known as aromatase inhibitors.

Antiarrhythmics: also known as antidysrhythmics, compounds used to stop arrhythmias, a loss of the normal rhythm of the heart including ectopic beats, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia and ventricular tachycardia. Antiarrhythmics were originally classified in 1970 into several classes by Vaughan Williams according to their effects on the electrical behaviour of myocardial cells and this classification remains despite some shortcomings. These are currently a total of 4 classes.
- Class I (further divided into Class Ia, Ib and Ic) are membrane stabilizing compounds which inhibit action potential propagation. These include sodium channel antagonists which act in the same way as local anaesthetics. Examples include quinidine, procainamide and disopyramide (Class Ia), lignocaine, phenytoin, tocainide and mexiletine (Class Ib) and flecainaide, encainide and propafenone (Class Ic).
- Class II are adrenoceptor antagonists which increase the refractory period of the AV node. Examples include propranolol, oxprenolol, pindolol and acebutolol.
- Class III  compounds which prolong the cardiac action potential duration and refractory period. Examples include amiodarone, sotalol and bretylium.
- Class IV are compounds which decrease the slow inward Ca2+ current which are voltage-sensitive calcium channel blockers acting on L-type channels by binding to the (α1 subunit and blocking the influx of calcium ions into myocardial cells. Calcium would normally bind to and inhibit the actions of troponin, a natural suppressor of muscle cell contraction. The inhibition of the actions of troponin prevents depolarization and cell contraction. Examples include verapamil and diltiazem but not the dihydropyridines.

Antiarthritics: compounds used to treat arthritis, inflammation of joints due to infiltration of immune cells and pro-inflammatory mediators. Antiarthritics include anti-inflammatory compounds such as NSAIDs, corticosteroids, DMARDs and immunosuppressants.

Antiasthmatics: compounds used to treat asthma, a breathing disorders in which there is reversible constriction of the trachea which can be fatal if untreated. These include bronchodilators (β2-adrenoceptor agonists and xanthines), H1 histamine receptor antagonists, muscarinic receptor antagonists, anti-inflammatory steroids and sodium chromoglycate).

Antibacterials: a type of antibiotic which are selectively toxic and used in the treatment of bacterial infections. These compounds are generally of low toxicity to humans due largely to the differences in physiology and biochemistry between humans and the microorganisms infecting them. They are classified in a variety of ways, ie according to the chemical class to which they belong, according to their affects against gram-positive and gram-negative bacteria and according to their natural, semisynthetic or wholly synthetic origin. They have several important mechanisms of action.
- Inhibition of cell wall synthesis - prevent the synthesis of the complex peptidoglycans found in bacterial cell walls. Examples include bacitracin, cephalosporins, penicillins, ristocetin and vancomycin.
- Inhibition of cell wall function - prevent the cell wall from carrying out its important function of a selective permeability barrier and allow ions and macromolecules to escape from the cell. Examples include amphotericins, colistin, imidazoles, nystatin and polymyxins.
- Inhibition of protein synthesis - prevent bacterial cells from synthesising proteins and thus disrupting cell function and reproduction. Examples include tobramycin, streptomycins, neomycin, kanamycin, gentamicin, tetracyclines, lincomycins, erythromycins and chloramphenicol.
- Inhibition of nucleic acid synthesis - prevent the reproduction of genetic material in bacterial cells. Examples include nalidixic acid, novobiocin, pyrimethamine, trimethoprim, rifampin and sulphonamides.

Antibiotic: a substance produced by microorganisms (bacteria and fungi), synthetic or semisynthetic compounds which kill or prevent the replication of other microorganisms. They are more selective than cytotoxic compounds. They can be natural products and are, for example, produced by bacterial of the genus Bacillus such as bacitracin, gramicidin and polymyxin and by Streptomyces such as streptomycin, tetracyclines and macrolides. Penicillium is an important fungal genus which produces penicillin and griseofulvin.
Natural and synthetic antibiotics fall into several classes for use in both humans and animals and the main classes are:

β-Lactams - includes the natural penicillins, semisynthetic penicillins, natural cephalosporins, semisynthetic cephalosporins, cephamycins, 1-oxacephems, clavulanic acids, penems, carbapenems, nocardicins and monobactam.
* tetracyclines, includes tetracyclines, anhydrotetracyclines and anthracyclines,
* aminoglycosides - includes noncyclitol aminoglycosides, neutral and monoaminocyclitol aminoglycosides, streptamine and related aminocyclitol aminoglycosides, 1,4-diaminocyclitol aminoglycosides and semisynthetic aminoglycosides,
* nucleosides
- includes C-nucleosides and carbocyclic nucleosides,
* macrolides - includes 12-, 14- and 16-membered ring macrolides,
* peptides - includes bleomycins, actaplanins, gramicidins, polymyxins, bacitracins and actinomycins,
* quinolones - includes nalidixic acid and first- and second- generation quinolones,
* sulphonamides,
* ansamycins
* amphenicols
* ionophore antibiotics- includes monensin, narasin and maduramicin.

Antibiotic resistance: resistance exhibited by an organism to the effects of antibiotics. The actions and main mechanisms of antibiotic resistance are shown in the table below. Resistance is usually divided into natural resistance (where the target bacteria has no transport system or lacks a target for a particular antibiotic) and acquired resistance (where changes take place in the bacterial genome such as mutation and selection or exchange of genes between strains and species).

Class of antibiotic
Mode of action
Resistance mechanisms
Cell wall biosynthesis inhibitors
eg piperacillin and ampicillin
Breakdown by β-lactamases
Altered penicillin binding protein targets
Altered bacterial permeability
Cell wall biosynthesis inhibitors
eg cefotaxime and cefadrine
Breakdown by β-lactamases
Breakdown by cephalosporinases
Cell wall biosynthesis inhibitors
eg cefoxitin
Breakdown by β-lactamases
Cell wall biosynthesis inhibitors
eg meropenem and imipenem
Breakdown by β-lactamases
Breakdown by dehydropeptidases
Cell wall biosynthesis inhibitors
eg aztreonam
Breakdown by β-lactamases
Cell wall biosynthesis inhibitor
eg vancomycin and teicoplanin
Alteration of target
DNA gyrase A and topoisomerase II inhibitors (preventing supercoiling)
eg norfloxacin and ciprofloxacin
Alteration of enzyme targets
Efflux pumps
Altered bacterial permeability
Protein biosynthesis inhibitors
eg amikacin and neomycin
Enzymatic modification of antibiotic (adenylated, phosphorylated or acetylated by target bacteria)
Alteration of ribosome target
Protein biosynthesis inhibitors Enzymatic modification of antibiotic (inactivated by chloramphenicol
Altered cell wall permeability
Protein biosynthesis inhibitors
eg erythromycin A, clarithromycin and azithromycin
Alteration of 23S rRNA
Enzymatic modification of antibiotic
Protein biosynthesis inhibitors
eg quinupristin and dalfopristin
Alteration of ribosome target
Active efflux
Enzymatic modification of antibiotic
Protein biosynthesis inhibitors
eg tetracycline and doxycycline
Efflux pumps
Alteration of ribosome target
Altered bacterial permeability
Enzymatic modification of antibiotic
Folic acid biosynthesis inhibitors Altered bacterial permeability
Folic acid biosynthesis inhibitor Altered bacterial permeability
Disruption of cell membrane structure
eg colistin (polymyxin E) and polymyxin B
Altered bacterial permeability

Antibloat agents: also known as viscosity-altering agents, substances which relieve the bloating caused by intestinal gas in animals. Examples include poloxalene, polymerized methyl silicone and vegetable oils such as soybean and peanut oil. These substances lower the surface tension of gas bubbles in the gut and break them up.

Antibody-directed enzyme prodrug therapy (ADEPT): a method of tumour drug therapy first described in 1987 involving treatment using an antibody-enzyme conjugate. The antibody is directed at a specific antigen present in the tumour tissue and the enzyme is one which is not usually present in the body. At a certain time after injection of this conjugate and after it has had time to concentrate itself at its target site, a prodrug is administered and, as this is a substrate for the enzyme, it is converted to a cytotoxic agent only in and around the target tissues. The consequence is a higher concentration of active drug at the target site and fewer systemic side effects.
Melton RG, Sherwood RF. Antibody-enzyme conjugates for cancer therapy. J Natl Cancer Inst (1996) 88; 153-165Bagshawe KD, Sharma SK, Springer CJ, Rogers GT. Antibody directed enzyme prodrug therapy (ADEPT). A review of some theoretical, experimental and clinical aspects. Ann Oncol (1994) 5; 879-891

Anticancers: also known as antineoplastics and antitumour agents, drugs used in the treatment of neoplastic diseases. They include a broad range of chemical classes with a variety of cytotoxic actions and, like antibiotics, can be classified according to their chemical class or according to their mechanism of action. When classified according to their mechanism of action they fall into the following general categories;
Alkylating agents alkylate DNA by forming covalent bonds with it in actively dividing tumour cells to prevent replication of genetic material. Examples include the nitrosoureas carmustine, lomustine and semustine and the nitrogen mustards cyclophosphamide, melphalan, ifosfamide, estramustine, and chlorambucil. Antineoplastic compounds possibly acting by alkylation include procarbazine, cisplatin, dacarbazine, hexamethylmelamine, and carboplatin.
Antimetabolites block one or more of the metabolic pathways involved in DNA replication and cell division. Examples include the folate antagonist methotrexate; purine antagonists such as mercaptopurine, thioguanine, cladribine, pentostatin and fludarabine; and pyrimidine antagonists such as fluorouracil, cytarabine, tomudex, gemcitabine and azacitidine.
- Other classes of antineoplastics include cytotoxic antibiotics, aromatase inhibitors, anti- oestrogens, ribonucleotide reductase inhibitors, biological response modifiers, antisense oligonucleotides, metalloprotease inhibitors, signal transduction inhibitors, tyrosine kinase inhibitors, farnesyl-protein inhibitors, telomerase inhibitors and miscellaneous agents including procarbazine, mitotane, amscarine, crisantaspase, asparginase, mitoxantrone, quinacrine and tegafur.

Anticestodal: drugs which kill tapeworms (Taenia) and commonly used in veterinary pharmacology. Examples include dichlorophen, benzimidazoles, eg mebendazole, fenbendazole and albendazole and praziquantel and epsiprantel. Mebendazole and albendazole have been used in humans to control hydatid cysts.
The mechanisms of action vary but dichlorophen causes uncoupling of oxidative phosphorylation in the tapeworm to deplete its ATP. Praziquantel caused paralysis of tapeworms probably by causing an increase in intracellular Ca 2+.

Anticholelithogenics: drugs which prevents the formation of gallstones. Examples include ursodiol and ursodeoxycholic acid.

Anticholesteremics: drugs which lower blood cholesterol levels. Several types of compound can do this including the HMG-CoA reductase inhibitors such as the statins (eg, atorvastatin, simvastatin and pravastatin), bile acid binding resins such as cholestyramine and colestipol, fibrates such as bezafibrate and clofibrate, ezetimibe (which inhibits intestinal absorption of cholesterol), nicotinic acids and fish oils containing omega-3-acid ethyl esters. See also antihypercholesterolaemics.

Anticholinergics: drugs which inhibit synaptic transmission of acetylcholine. They include muscarinic and nicotinic receptor antagonists and acetylcholine synthesis inhibitors.

Anticholinesterases: drugs which reversibly or irreversibly block the actions of cholinesterases (enzymes which inactivate acetylcholine). They are classified into centrally acting and peripherally acting.
- Peripherally acting anticholinesterases are divided into three groups, ie short-acting, medium-duration and irreversible and this classification is dependent on the way in which they interact with this enzyme. They tend to inhibit acetyl- and butyrylcholinesterases about equipotently.
- Short-acting compounds bind only to the anionic site of this enzyme which is present at the neuromuscular junction. Their duration of action is very brief because the ligand-enzyme bond formed is easily reversed making them of no therapeutic value. Examples include edrophonium.
- Medium-acting compounds contain strongly basic groups which bind to the anionic site of acetylcholinesterase.

Anticoagulants: drugs which inhibit the coagulation of blood. They act by a variety of mechanisms. For example, coumarin derivatives such as bishydroxycoumarin and warfarin inhibit the synthesis of prothrombin, heparin which is a polysaccharide acts by preventing prothrombin formation, by preventing the formation of fibrin another clotting substance, and by decreasing the availability of thrombin. They are used clinically to treat thrombosis and thrombotic disorders like deep vein thrombosis.

Anticoccidials: drugs used to treat coccidiosis, a protozoal infection which infects the intestine and prevalent in a wide range of animals including calves, piglets and poultry. Examples of anticoccidial agents include decoquinate, amprolium, nicarbazin and metronidazole. Vaccines are also used in the treatment of coccidiosis.

Anticolitis agents: drugs used to treat colitis, ie inflammation of the colon which includes ulcerative colitis, inflammatory bowel disease and Crohn's disease. Examples include sulphasalazine and olsalazine.

Anticonflict test: see Vogel's anticonflict test.

Anticonvulsants: also known as anti-epileptics, drugs which inhibit seizures, ie partial seizures, generalized seizures, status epilepticus and febrile convulsions. Examples include carbamazepine, gabapentin and lamotrigine.

Antidepressants: also known as thymoloeptics, drugs which relieve the symptoms of depressive illness. They were originally developed in the early 1950 and have been used ever since. Examples include chlorpromazine, imipramine, amitriptyline, maprotiline, fluoxetine and paroxetine.

Antidiabetics: drugs used to treat diabetes mellitus. Examples include insulin and oral hypoglycemics such as sulphonylureas, eg glibenclamide and glicazide, biguanides, eg metformin and other antidiabetics such as ararbose and nateglinide.

Antidiarrhoeals (antidiarrheals): also known as antiperistaltics and antimotility drugs, drugs used to treat diarrhoea both prophylactically and symptomatically. Examples include codeine phosphate and loperamide hydrochloride.

Antidiuretics: drugs which inhibit diuresis, ie the formation of urine. Examples include desmopressin (an analogue of vasopressin and used to treat diabetes insipidus).

Antidiuretic hormone (ADH): also known as vasopressin, a nonapeptide secreted by the posterior pituitary gland. It is a potent vasoconstrictor which produces a sustained increase in permeability of the nephron facilitating the passive reabsorption of water from the urine back into the blood. ADH acts via vasopressin receptors the main actions of vasopressin on the kidney being mediated by V2 receptors. Clinically ADH is used to treat pituitary (cranial) diabetes insipidus and bleeding from oesophageal varices.

Antidiuretic hormone antagonist: drugs which antagonise the effects of antidiuretic hormone and so prevent it from causing the reabsorption of water from the nephron back into the blood. Examples include conivaptan which has an aquaretic effect, ie increases the loss of water from the kidneys.

Antidote: a drug which is administered to counteract the effects of a poison. They act via a variety of mechanisms such as enzyme reactivation, enzyme inhibition and competitive receptor antagonism. Examples include the use of naloxone to antagonize the effects of opioid poisoning, pralidoxime which reactivates cholinesterase after organophosphorus cholinesterase inhibition, vitamin K which acts as an enzyme substrate in warfarin poisoning and oxygen which is given for carbon monoxide poisoning as it competes with carbon monoxide for binding sites in haemoglobin.

Antidromic: nerve conduction where impulses travel in the opposite direction to normal.

Antidyskinetics: drugs used to treat dyskinesias such as Parkinson's disease and drug-induced extrapyramidal effects. Examples include biperiden, procyclidine, trihexyphenidyl, and benztropine.

Antieczematics: drugs for the local treatment of eczema, a skin disease also referred to as dermatitis. Examples include coal tar ointment.

Antiemetics: also known as antinauseants, drugs which suppress the vomiting reflex. Examples include H1 histamine receptor antagonists such as cyclizine, diphenhydramine and meclizine, dopamine antagonists such as chlorpromazine, metoclopramide and domperidone and the 5HT3 antagonists granisetron, ondansetron and dolasetron. Antiemetics are usually used for the treatment of motion sickness.
Antiepileptics: also known as anticonvulsants.

Anti-estrogens: see anti-oestrogens.

Antifibrinolytics: drugs which inhibit fibrinolysis, ie the breakdown of fibrin clots (formed naturally to prevent blood loss) and so compounds which reduce bleeding. They are used in surgery to promote haemostasis and clinically to treat blood loss after tooth extraction and in mennorrhagia. Examples include (-aminocaproic acid, tranexamic acid, aprotinin and etamsylate.

Antifibrotics: drugs which causes the regression of fibrosis which is the formation of fibrous tissues. Fibrous tissues are mainly made up of type I collagen many drugs potentially affect fibrosis and include cytokine inhibitors such as TGF-β antagonists, phosphodiesterase inhibitors, antioxidants such as silymarin, metalloprotease inhibitors such as halofuginone, prostanoids such as PGE2 and vasoactive modulators such as ACE inhibitors enalapril and captopril.

Antiflatulent agents: drugs used for the alleviation or prevention of flatulence, ie excessive intestinal gas. Examples of antiflatulent agents include simethicone (an antifoaming agent).

Antifolates: also known as folate antagonists, antimetabolite compounds which interfere with the normal metabolism of folic acid which is necessary in the formation of nucleotides. They are usually used in the treatment of cancer such as leukaemia. Examples include methotrexate which binds almost irreversibly to and inhibits dihydrofolate reductase, an enzyme essential in the synthesis of purine and pyrimidine DNA bases, preventing the formation of the coenzyme tetrahydrofolic acid.

Antifungals: also known as antimycotics, drugs which inhibit the proliferation of fungal cells or which kill them. Almost all antifungal drugs act by interfering with fungal cell wall synthesis. The cell wall comprises three main components; chitin (the synthesis of which is inhibited by chitin synthase inhibitors), glucan (the main component inhibited by glucan synthesis inhibitors) and mannoprotein binders. Antifungals are divided into several classes including polyenes, allylamines, imidazoles, thiocarbamates and azoles. They are used clinically to treat fungal disorders such as Candida albicans infections of the skin and mucous membranes, systemic yeast and fungal infections, invasive aspergillosis, cryptococcal meningitis and dermatophyte infections.

Antiglaucoma: drugs used to treat glaucoma, a disorder of the eyes characterized by a rise in ocular pressure and atrophy of the optic nerve. A variety of drugs are used including β-adrenoceptor antagonists such as betaxolol and timolol, topical carbonic anhydrase inhibitors such as dorzolamide and brinzolamide, a2-adrenoceptor stimulants such as brimonidine and apraclonidine and prostaglandin analogues such as latanoprost.

Antigonadotropins: drugs which inhibit the secretion or actions of gonadotropins, ie hormones which stimulate the gonads such as follicle-stimulating hormone and leutenizing hormone. Antigonadotropins are used to . Examples include danazol (used clinically to treat endometriosis, severe pain and tenderness in benign fibrocystic disease and hereditary angioedema), buserelin (used clinically against endometriosis) and leuprolide (used for the clinical treatment of endometriosis and to reduce the size of uterine fibroids prior to surgery).

Antigout: drugs used to treat gout, an inflammatory condition caused by the accumulation of uric acid crystals in joints such as those of the toes causing intense pain and restrictions in movement. Antigout treatment largely comprises uricosurics (drugs which promote the excretion of uric acid via the kidneys) such as allopurinol, colchicine and non-steroidal anti-inflammatory drugs. See under allopurinol for uric acid metabolism.

Antihelminthic: also known as helminthicidals, drugs used to treat helminth infections including infections by tapeworms (cestodes), intestinal roundworms (nematodes), trematodes (flukes), tissue roundworms and hydatid tapeworms Antihelminthic agents also act against hydatid disease, schistosomal infections and filarial infections. Examples include mebendazole, piperazine, niclosamide, albendazole and ivermectin.

Antihaemorrhagic: also known as haemostatics, drugs which stop bleeding. Examples include aprotinin, desmopressin, etamsylate and traxenamic acid. They are generally used to control blood loss during surgery and in the treatment of haemophillia.

Antihistamines (antihistaminics): drugs which counteract the actions of histamine and which are used clinically to treat allergies of the skin and eye, allergic rhinitis, urticaria, pruritis, eczema, insect bites and stings, drug allergies, nausea, vomiting and vertigo. Examples include acrivastine, cetirizine, chlorphenamine, cyproheptadine and promethazine.

Antihyperalgesics: drugs which inhibit the development of hyperalgesia which is extreme sensitivity to pain. Examples of antihyperalgesics include morphine, buprenorphine and dezocine.

Antihypercholesterolaemics: drugs used to treat abnormally high levels of cholesterol in the blood. Examples include HMG-CoA reductase inhibitors such as atorvastatin, simvastatin and pravastatin, bile acid binding resins such as the anion-exchange resins cholestyramine and colestipol, fibrates such as bezafibrate, gemfibrozil and clofibrate, nicotinic acid, ezetimibe (which inhibits the intestinal absorption of cholesterol) and fish oils such as omega-3-acid ethyl esters. Antihyperglycaemics: drugs which lower blood glucose levels. Examples include insulin, insulin sensitizers, PPAR agonists, sulphonylureas such as glibenclamide, glipizide and tolbutamide, biguanides such as metformin as well as acarbose, nateglinide, pioglitazone and rosiglitazone.

Antihyperlipidemics: drugs which lower blood lipid levels. They act in a variety of ways and include statins, fibrates, nicotinic acid, squalene synthase inhibitors, CETP inhibitors,  bile acid sequestrants and phytosterols. They are used to treat hyperlipidaemia.

Antihyperlipoproteinaemics: also known as antihyperlipidemics.

Antihyperphosphataemics: drugs used to lower blood phosphate levels. Examples include phosphate-binding agents such as aluminium hydroxide and sevelamer.

Antihypertensives: drugs which lower blood pressure. They do this by a variety of mechanisms and include potassium channel activators, adrenergic neurone blockers, vasodilators, adrenergic transmitter depletors, ganglion blockers and α1- adrenoceptor antagonists.

Antihyperthyroids: compounds which decrease or antagonize the effects of thyroid hormones in endocrine disorders such as hyperthyroidism and thyrotoxicosis. Examples of antihyperthyroid drugs include carbamizole, iodine and iodide and propylthiouracil.

Antihypoglycaemics: drugs which lower the blood sugar levels and which are used clinically to treat diabetes mellitus both insulin-dependent and non insulin-dependent types. Examples include insulins which promote the formation of glucagon in the tissues from glucoses in the blood, oral antidiabetic drugs including he sulphonylureas such as chlorpropamide, glibenclamide and glipizide (which augment insulin secretion) , the biguanides such as metformin (which decreases gluconeogenesis) and other antidiabetics such as acarbose (which inhibits intestinal α-glucosidase and slows the absorption of starch and glucose) and the thiazolidinediones nateglinide and pioglitazone (which reduce peripheral insulin resistance).

Antihypotensives: drugs which inhibit a fall in blood pressure and used clinically to treat hypotension. Examples include the vasoconstrictor sympathomimetics ephedrine, metaraminol, noradrenaline acid tartrate and phenylephrine. They are used clinically to treat acute hypotension and act by agonizing α-adrenoceptors causing vasoconstriction.

Antihypothyroids: drugs used to treat a deficiency in thyroid hormones, ie hypothyroidism. Examples include levothyroxine and liothyronine which are used to treat myxoedema, diffuse non-toxic goitre, Hashimoto's disease (lymphadenoid goitre) and thyroid carcinoma.

Anti-ictals: drugs used to treat ictogenesis which is the initiation and spread of a single epileptic seizure.

Anti-infectives: drugs used to treat infections by bacteria (antibacterials and antibiotics), fungi (antifungals) and viruses (antivirals).

Anti-inflammatory: compounds used to treat inflammation, a cytological and chemical reaction affecting blood vessels and adjacent tissues such as joints in response to injury or stimulation by chemical, physical or biological agents. Anti-inflammatory agents comprise NSAIDs, steroids, DMARDs and antigout agents.

Antileishmanials: also known as leishmanicidals, drugs used to treat infections caused by single cell organisms of the genus Leishmania which are transferred to humans and animals by sandflies. Examples of antileishmanials include sodium stibogluconate and meglumine antimonate both pentavalent antimony compounds used in humans to treat leishmaniasis.

Antileprotics: drugs used to treat leprosy (Hansen's disease), a chronic granulomatous infection caused by Mycobacterium leprae which causes damage to the skin, nerves and testes. Examples include dapsone, rifampicin and clofazimine of which rifampicin and dapsone are use for both types of leprosy, ie multibacillary leprosy and paucibacillary leprosy.

Antilibidinals: drugs used reduce libido and to treat patients with disorders of sexual thoughts, urges, or acts. Examples include cyproterone acetate and medroxyprogesterone acetate.

Antilipidaemics: also known as antihyperlipoproteinaemics and antihyperlipidaemics.

Antimalarials: drugs with activity against the protozoal parasites causing malaria (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariea). Examples include quinoline-methanols such as quinine and mefloquine, 4-aminoquinolines (eg chloroquine and amodiaquin), 8-aminoquinolines (primaquine), 9-aminoacridines (mepacrine), biguinides (proguanil) and sulphones (dapsone and acedapsone).

Antimanics: also known as mood stabilizers.

Antimetabolites: a class of anticancer compounds which are in some way structurally analogous to components required for cell division and which inhibit cell division because they take the place of natural substrates in cell biochemical reactions. They act by competitive inhibition to impair DNA synthesis. Examples include the folate antagonist methotrexate, the pyrimidine analogue 5-fluorouracil and the purine analogue 6-mercaptopurine.

Antimicrobials: drugs for the treatment of microbial infections, ie infections causes by bacteria, fungi and viruses. See also antibiotics.

Antimigraines: drugs used to treat migraine, ie an intense and disabling headache which has a vascular origin. Antimigraines comprise simple analgesics such as aspirin, paracetamol and tolfenamic acid, 5-HT1 agonists such as the triptans including almotriptan, eletriptan and sumatriptan and ergot alkaloids such as ergotamine.

Antimitotics: drugs which inhibit cell division of somatic, ie non-sex cells. They include spindle poisons such as colchicin

: drugs containing antimony which were once used to treat schistosomiasis, filariasis and leishmaniasis.

Antimuscarinics: also known as muscarinic receptor antagonists.

Antimycobacterials: drugs used to treat mycobacterial infections, ie infections caused by organisms such as Mycobacterium tuberculosis and Mycobacterium leprae (which cause tuberculosis and leprosy). Antimycobacterial drugs include isoniazid, rifamycin and streptomycin for the treatment of tuberculosis and dapsone for the treatment of leprosy.

Antimycotics: also known as antifungals.

Antinauseants: also known as antiemetics.

Antinematodals: also known as nematocides.

Antineoplastics: also known as anticancers.

Antinociceptives: drugs used to treat pain. Examples include opioid analgesics such as morphine, buprenorphine, diamorphine (heroin) and fentanyl, the non-opioid analgesics such as aspirin, paracetamol and nefopam and drugs to treat neuropathic pain such as amitryptyline and gabapentin.

Anti-oestrogens (anti-estrogens): compounds which antagonize the effects of oestrogens and which are commonly used to treat hormone-dependent tumours such as those of the breast. Examples include tamoxifen (used clinically to treat breast cancer and anovulatory infertility) and toremifene (used clinically to treat hormone-dependent metastatic breast cancer in postmenopausal women). These compounds bind to oestrogen receptors and inhibit oestrogen-induced tumour cell proliferation.
Wolf DM, Fuqua SA. Mechanisms of action of antiestrogens. Cancer Treat Rev (1995) 21; 247-71

Anti-osteoporotics: also known as bone resorption inhibitors, antipagetics and calcium regulators, compounds used in the treatment of osteoporosis which is a progressive weakening of the bones due to loss of calcium from the bone matrix.

Antipagetics: also known as anti-osteoporotics.

Antipain: a low molecular weight oligopeptide-fatty acid compound obtained from microbes. It irreversibly activates proteases and has been used to treat pain. Antipain inhibits papain, trypsin and plasmin.
Nitu A et al. Emerging trends in the pharmacotherapy of chronic pain. Expert Opin Investig Drugs (2003) 12(4); 545-559

Antiparasitics: compounds used for the treatment of parasitic disease. Examples include drugs for the treatment of helminth infections and are used in both humans and animals.

Antiparkinsonians: drugs used in the treatment of Parkinson's disease which is a motor disorder caused by degeneration of certain parts of the brain particularly the substantia nigra and characterized by trembling and poorly controlled motor movements. Examples of antiparkinsonian drugs include levodopa, amantadine, selegiline and pramipexole. They act by enhancing dopaminergic activity in the brain.

Antiperistaltics: also known as antidiarrhoeals.

Antiplatelets: drugs which inhibit the coagulation of platelets and which are used clinically to treat thrombosis particularly in arterial circulation where anticoagulants have little effect. Examples include abciximab, aspirin, clopidogrel, dipyridamole, eptifibatide and tirofiban.

Antiprogestogens: drugs which inhibit the effects of progestogen and which usually have anti-fertility actions. Examples include mifepristone (RU-486), They have been used in emergency contraception such as the morning after pill.

Antiprotozoals: compounds used to kill protozoa such as Eimeria spp., the causative agent of coccidiosis and commonly used in veterinary pharmacology.

Antipruritics: drugs which stop itching (pruritis) and its symptoms. Examples include topical antihistamines such as mepyramine, diphenhydramine and antazoline often given together with and mint, menthol or camphor. Other examples include calamine, crotamiton and doxepin hydrochloride and local anaesthetics such as tetracaine and benzocaine.

Antipsychotics: also known as neuroleptics and major tranquilizers, drugs used to treat psychoses, ie schizophrenia, affective disorders such as depressive illness and mania, and organic psychoses such as mental disorders caused by head injury or alcoholism. Antipsychotics are classified into classical antipsychotics (also known as typical antipsychotics) and atypical antipsychotics largely according to the incidence of extrapyramidal side effects (fewer with atypical drugs), their effects in patients who have become resistant to treatment and their effects against negative symptoms such as withdrawal from social contact and suppression of emotional responses. The classical group includes many compounds developed before the 1980s such as chlorpromazine (a phenothiazine), haloperidol (a butyrophenone), thioridazine (a phenothiazine) flupenthixol and clopenthixol. The atypical group includes clozapine (a dibenzodiazepine) and sulpiride (a benzamide).

Antipanic: drugs for the treatment of panic, an anxiety disorder which is treated clinically with long-term administration of tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors such as phenelzine or with selective serotonin reuptake inhibitors (SSRI).

Antipyretics: compounds which lower body temperature and thus reduce fever. Examples include aspirin and paracetamol.

Antipyrine: also known as phenazone, a compound used to measure the ability to metabolize drugs since it is readily absorbed from the gut, less than 10% is protein bound and it is extensively metabolized (~95%) by the mixed-function enzyme system.

Antirachitics: compounds used to treat rickets, a disorder of the bones caused by vitamin D deficiency and characterized by deficient calcification of bone tissue. Examples of antirachitics include mineral supplements and oral supplements of vitamin D or a derivative such as calcitriol or alfacalcidol although rickets is rare in Western countries due to good nutrition.

Antiresorptives: compounds which inhibit the resorption of bone, ie the breakdown of bone to release calcium into the blood and so compounds which increase bone mass by inhibiting osteoclast function. Examples include the bisphosphonates, oestrogen, raloxifene and salmon calcitonin.

Anti-retroviral therapy (ART): treatment of viral infections with antiviral compounds including stavudine, zidovudine and tenofovir. ART forms 1st line therapy for HIV infections.

Antirickettsials: compounds used to treat infections caused by bacteria of the genus Rickettsia which are carried by ticks, fleas and mites. These organisms cause typhus fever, Q-fever, Rocky mountain spotted fever, rickettsial pox, trench fever, trachoma and psittachosis amongst others. Antirickettsial drugs include tetracyclines such as tetracycline, doxycycline and minocycline and chloramphenicol and co-trimoxazole.

Antiriot agent: also known as tear gas, these agents are potent lachrymators and irritants which have been used for riot and crowd control since the early 1960s. The most widely used is CS gas (chlorobenzylidenemalononitrile, first developed in 1928) which, in aerosol form, causes irritation of mucous membranes such as in the eye, nose and throat and irritation of the skin. The consequence of exposure to CS gas is severe lachrymation, coughing and vomiting but, as the lethal dose is very high, this agent is considered to be reasonably safe. Tear gas was originally used by Paris police in 1912 when the used ethyl bromoacetate in riot control and although antiriot agents were developed throughout World War I few were used in public although CS and CN (ω-chloroacetophenone) have been used.

Antischistosomals: compounds used to treat infections of schistosomes, a genus of trematodes worms and flukes which include blood flukes and which can be carried by water snails (bilharzia being a common schistsomal infection in tropical countries). Antischistosomals include praziquantel.

Antisense oligonucleotides (ANO): short oligonucleotide fragments composed of single-stranded RNA or DNA. They bind to specific DNA or RNA sequences to which they are complimentary thus preventing the expression of that nucleic acid sequence. Commonly, mRNA fragments are used to halt the expression of proteins.

Antiseptics: compounds which non-selectively kills or inhibits the growth of a wide variety of microorganisms. Antiseptics are usually too toxic to be used for internal use in humans but can be used topically on the skin to sterilize wounds or to prepare aseptic surfaces such as floors and benches.

Antiserum (pl. antisera): also known as immune serum, the serum of a human or animal which has been immunized against an antigen, ie serum which contains antibodies to the antigen along with other serum proteins.

Antisickling agents: also known as desickling agents, agents used to prevent or treat sickling of erythrocytes in sickle cell disorders such as sickle cell anaemia. Sickling is a disorder where sickle haemoglobin (HbS, a variant of haemoglobin with an amino acid alteration in the β-chain of Hb) polymerizes causing erythrocytes to undergo cell deformation (sickling) when deoxygenated and so these cells lose their ability to carry oxygen. Examples of antisickling agents include hydroxyurea, dibromoaspirin, decitabine and short-chain fatty acids.

Antispasmodics: compounds used to treat muscle spasms, sudden involuntary contractions of one or muscles which include cramps and contractures. Antispasmodic therapy depends on the muscles affected by the spasm but include muscarinic receptor antagonists such as atropine, hyoscine and propantheline for the symptomatic relief of gastrointestinal spasm.

Antispastic: a drug used to treat muscle rigidity and spasticity. Examples include baclofen.

Antisympathetic agents: drugs used to abolish the effects of the sympathetic nervous system. Examples include clonidine.

Antithrombins: compounds which inhibit thrombin, an enzyme that converts fibrinogen into fibrin causing fibrin deposition in blood clots.

Antithrombotics: compounds used to prevent and treat thrombosis, the formation or presence of a blood clot in the cardiovascular or cerebrovascular systems which can cause infarction of affected tissue. Antithrombotic therapy comprises heparin and heparinoids, hirudins, oral anticoagulants such as warfarin and platelet aggregation inhibitors such as aspirin, clopidogrel and ticlopidine.

Antithyroid agents: also known as goitrogens, compounds used to treat hyperthyroidism (excessive production of thyroid hormone) which causes the onset of goitre. Goitrogens include the antidysrhythmic amiodarone.

Antitrematodal: compounds which kills liver (eg Fasciola hepatica) and lung flukes and used commonly in veterinary pharmacology. Examples include albendazole, praziquantel and clorsulon. The mechanisms of action vary but clorsulon inhibits 3-phosphoglycerate kinase and phosphoglyceromutase in the glycolytic pathway so depriving flukes of their metabolic energy.

Antitrypanosomal agents: compounds used to treat trypanosomal infections, ie protozoan flagellates which are parasitic in human and animal blood and which are often carried by an intermediate host such as a leech, tick or insect. Tsetse flies are typical vectors. Common antitrypanosomal therapy depends on the strain of organism causing trypanosomiasis.

Antitubercular agents: agents use in the treatment of tuberculosis, a mainly pulmonary disease caused by Mycobacterium tuberculosis and which can be fatal if not treated. Examples of antitubercular drugs include isoniazid with or without rifampicin for the prophylaxis of tuberculosis and isoniazid, rifampicin, ethambutol and pyrazinamide for the treatment of tuberculosis. The successful outcome of which depends on the specified drug regimen used.

Antitubulin agents: compounds which bind to or otherwise inhibit the actions of tubulin, a cellular material important for chromosome segregation during cell division, internal transport, cell motility and the development and maintenance of cell shape. Antitubulin agents inhibit cell division and have anticancer actions. Examples include vinca alkaloids such as vincristine, vinblastine, vindesine and vinorelbine, podophyllotoxins, camptothecins, and taxoids such as paclitaxel and docetaxel.

Antitumour agents: also known as antineoplastics.

Antitussives: compounds which prevent tussis, ie coughing. They may facilitate the removal of sputum (expectorants), they may be non-narcotic suppressants of the cough reflex (such as noscapine and benzonatate) or may be a narcotic analgesic which depresses the cough reflex (such as codeine and dextromethorphan).

Antiulcerogenics: agents which prevent the development of ulcers.

Antivenins: also known as an antivenoms, substances produced to counteract the effects of venoms.

Antiviral: compounds used to prevent and treat infections caused by viruses. Antivirals act by a range of mechanisms.
- Inhibitors of virus adsorption inhibit interaction between the virus envelope and receptors on the host cell surface. Examples include polyanions such as dextran sulphate, zintevir and suramin.
- Virus-cell fusion inhibitors prevent the lipid bilayers in the virus from fusing with the outer cell membrane of the host cell. Examples include negatively charged albumins such as Suc-HAS, oligopeptides such as pentafuside T20 and bicyclam derivatives such as AMD 3100.
- Virus uncoating inhibitors prevent for virus from disassembly once inside the host cell so that its nuclear material cannot enter the host cell nucleus. Examples include cyclosporin A analogues, ADA and dithiobisbenzamides such as SRR-SB3.
- Reverse transcriptase inhibitors prevent this enzyme from catalysing the conversion of single-stranded viral RNA to double-stranded proviral DNA which is subsequently integrated into the genome of the host cell. Examples include nucleoside reverse transcriptase inhibitors such as AZT, DDI and DDC, nucleotide reverse transcriptase inhibitors such as acyclic nucleoside phosphonates PMEA and PMPA. Non-nucleoside reverse transcriptase inhibitors such as nevirapine, delaviridine and loviride.
- Inhibitors of proviral DNA transcription to mRNA include benzodiazepines such as Ro 5-3335, peptoids such as CGP 64222 and adenosine analogues such as nephlanocin A.
- Viral mRNA inhibitors prevent the expression of viral protein in the host ribosomes and examples include ribozymes and antisense oligonucleotides.
- Viral maturation inhibitors prevent the virus from assembly into its final stage following modifications to its protein components. Examples include proteolysis inhibitors such as saquinavir, ritonavir and indinavir, and viral protein modification inhibitors such as glycosylation inhibitors and myristoylation inhibitors.

Anuran skin alkaloid: usually toxic alkaloids present in the skins of frogs and toads belonging to the order Anura. These are tail-less amphibians with long hind legs specialized for hopping and include poisonous frogs from which batrachotoxins, pumilotoxins, histrionicotoxins, epibatine, pseudophrynamines and other alkaloids are derived. The toxins in these frogs are not synthesized by the animals themselves but are assimilated from their diets of ants, beetles and centipedes (captively-raised anuran frogs do not have toxic alkaloids in their skin).

Anxiogenic: inducing a state of anxiety or panic disorder. Several activities are used to induce anxiety in animals such as the elevated plus maze and forced swimming test in order to investigate the anxiolytic effects of drugs. Examples of anxiogenic drugs include CGS 8216 (a high affinity ligand for the GABAA/benzodiazepine receptors) , picrotoxin and yohimbine.

Anxiolytics: drugs used to treat anxiety including phobias, anguish and panic attacks. Examples include benzodiazepines such as diazepam, alprazolam and lorazepam, buspirone, β-blockers (which reduce autonomic symptoms such as palpitations and tremor), meprobamate and barbiturates.

Apamin: an 18 amino acid highly neurotoxic protein from the venom of honey bees (Apis mellifera). It is known to cause hyperexcitability, convulsions and respiratory paralysis in animals by blocking small conductance Ca2+-activated K+ channels.

Apelin peptides: peptides related to cardiovascular function and fluid homeostasis.

Aperient: also known as a laxative, a drug which facilitates the evacuation of the bowels.

Apomorphine: an alkaloid and potent D2 dopamine receptor agonist. It is an emetic acting via the chemoreceptor trigger zone and is used experimentally to induce vomiting in animals such as dogs in order to test the effects of antiemetics. It is also used in veterinary pharmacology to induce vomiting in dogs after accidental ingestion of a poison.
Suppression of vomiting induced by apomorphine is a measure of the D2 antagonism of the test drug. Typically, the test drug is given 2 hours after a dose of apomorphine (0.3mg/kg) to animals such as beagle dogs subcutaneously. The frequency of vomiting is then used to assess the potency of D2 antagonism by the test compound.

Apoptosis: also referred to as programmed cell death, a process in which cells die. in a regulated manner which is controlled genetically. Apoptosis in a normal event observed in embryonic development, immune cell differentiation and metamorphosis. It is carefully regulated by genes and their products such as p53.

Apoptosomes: multimeric protein complexes which mediate the activation of an initiator caspase at the onset of apoptosis (programmed cell death). Adams JM, Cory S. Apoptosomes: engines for caspase activation. Curr Opin Cell Biol (2002) 14(6);715-20

Apoptosome inhibitors: compounds which inhibit the formation and/or function of apoptosomes. Examples include the oncoprotein prothymosin-α.

a posteriori: the process of predicting causes by observing their effects or outcomes. Also referred to as inductive reasoning.

Appetite suppressants: drugs which decrease the desire to eat and are which are used in the short-term treatment of obesity. Examples include benzphetamine, diethylpropion, mazindol, phendimetrazine and phentermine.

Aprotinin: a proteolytic enzyme inhibitor which acts on plasmin and kallikrein to inhibit fibrinolysis. It is used to treat major blood loss during or after surgery such as open heart surgery.

APUD: amine precursor uptake decarboxylase system.

Aquaresis: the selective loss of water through the kidneys.

Aquaretic: drugs which cause water loss through the kidneys and which are used to treat hypertension and oedema. Examples include niravoline and the non-peptide antidiuretic hormone V2 receptor antagonists OPC-31260.

Arachidonic acid: a membrane-bound 20-carbon unsaturated fatty acid (all-cis-5,8,11,14-eicosatetraenoic acid) which is the starting material for the synthesis of prostaglandins, thromboxanes, leukotrienes, lipoxines, isoprostanes clavulones and punaglandins. Arachidonic acid is a common constituent present in the phospholipids present in cell membranes and is release by the action of phospholipase A2.

Arachidonyl-2-chloroethylamide (ACEA): a cannabinomimetic.

ARB: angiotensin receptor blocker.

ARC 239: a selective antagonist of α2B-adrenoceptors.

ARE: a symbol used in pharmacokinetics to denote the amount of drug remaining to be excreted in the urine and shown in mg or μmole.

Area under the curve (AUC): the area under the curve of a graphical plot of plasma concentration of a drug against time after its administration is referred to as the AUC and is an indication of the total amount of a drug in the body at any particular time point. It is shown in units of mg-hr/L or μM-hr. AUC also represents both the total amount of drug absorbed and the total amount eliminated. It can be used to estimate important pharmacokinetic parameters such as total clearance of the drug, its volume of distribution as well as the absolute and relative bioavailability. Comparisons of AUCs for different drug preparations can be used to compare bioequivalence. The area can be calculated or may be approximated using the trapezoidal method. A total area from time 0 to infinity is implied unless it is otherwise stated.

Area under the first moment curve (AUMC): the total area under the first moment-time curve shown in units of mg-hr2/L or μM-hr2.

Ariens, EJ: Dutch pharmacologist.

ARL 67156: also known as FPL 67156, a selective ecto-ATPase inhibitor (6-N,N-diethyl-β-γ-dibromomethylene-D-adenosine-5'-triphosphate trisodium salt).

ARMI: age- related memory impairment.

Aromatases: enzyme complex which catalyze the aromatization of the A ring in steroids during the conversion of androgens to oestrogens. They are important in reproduction and in the development of hormone-dependent tumours.
Conley A and Hinshelwood M. Mammalian aromatases. Reproduction (2001) 121; 685-695

Aromatase inhibitors: also known as anti-aromatases, compounds which inhibit the cytochrome P450 component of the aromatase enzyme complex and so inhibiting the biosynthesis of oestrogens in peripheral tissues. Aromatase inhibitors can be broadly divided into two groups. Type I inhibitors (also known as aromatase inactivators) have a steroidal structure similar to androgens and irreversibly inactivate the enzyme by blocking the substrate-binding site. Type II inhibitors are non-steroidal and they are reversible. Aromatase inhibitors can also be divided into first-generation inhibitors such as aminoglutethimide, second-generation such as formestane and fadrazole and third-generation anastrozole, letrozole, and exemestane. Third-generation aromatase inhibitors are being investigated for use as first-line and second-line therapy in oestrogen receptor- and progesterone receptor-positive advanced breast cancer in postmenopausal women.
Mokbel K. The evolving role of aromatase inhibitors in breast cancer. Int J Clin Oncol (2002) 7(5); 279-83

Aromatic L-amino acid decarboxylase
: an enzyme (EC also known as DOPA decarboxylase which catalyses the decarboxylation of DOPA to form dopamine. It is present in the cytosol of serotoninergic, histaminergic, adrenergic, noradrenergic and dopaminergic neurones, its is a relatively non-specific enzyme and because it is not a rate-limiting enzyme its inhibition is not an effective means of regulating neurotransmitter production.

Arphamenines: a group of small peptide inhibitors of aminopeptidases. Examples include arphamenine A, an Arg-Phe analog without a peptide bond and an aminopeptidase B inhibitor.

Arrestins: a family of inhibitory proteins which bind to agonist-activated, tyrosine phosphorylated receptors blocking their interaction with G-proteins and thereby terminating signalling. They compete with transducin for light activated rhodopsin in the eye, thus inhibiting the response to light and immune responses to arrestin lead to autoimmune uveitis. Arrestins are signal transduction modulators, which include visual arrestins, β-arrestin-1, and β-arrestin-2, are believed to play an important role in regulation of desensitization of G protein-coupled receptors.

Arsenicals: a class of compounds containing arsenic and formerly used to treat trypanosomal and leishmanial infections. The first one use clinically was arsphenamine (Salvarsan) for the treatment of syphilis. They were used from about 1908 to the 1950s but their use faded thereafter due to the development of safer and more potent drugs.

ART: anti-retroviral therapy

Arylacetic acid derivatives: a class or non-steroidal anti-inflammatory drugs. Examples include indomethacin, sulindac and diclofenac.

Arylbutyric acid derivatives: a class of non-steroidal anti-inflammatory compounds. Examples include fenbufen, butibufen and xenbucin.

Arylcarboxylic acids: a class of non-steroidal anti-inflammatory compounds. Examples include clidanac and ketorolac.

Arylethanolamines: a class of antihypertensive compounds which include labetalol, sotalol and sulfinalol. The arylethanolamine moiety is shown in blue.

Aryloxyalkylamines: a diverse class of compound which includes antidepressants (an example is fluoxetine). Some β-blockers such as propranolol and pindolol are also aryloxyalkylamines.

Aryloxypropanolamines: a class of antihypertensive compounds which include atenolol, nadolol, propranolol, acebutolol and pindolol. They all include the aryloxypropanolamine structure shown in the figure in blue.


Arylpropionic acid derivatives: a class of non-steroidal anti-inflammatory compounds. Examples include ibuprofen, naproxen, fenoprofen, flurbiprofen and oxaprozin. The arylpropionic acid moiety is shown in blue.

arylpropionic acids

Ascaricides: (not to be confused with acaricides) compounds for the treatment of ascarid nematodes infestations such as common roundworm infections (caused by Ascaris lumbricoides). Examples of ascaricides include levamisole (a nicotine-like nematocide used to treat microfilaricidal infections and as a cattle wormer which acts by paralyzing worms by depolarizing neuromuscular block), mebendazole and piperazine.

Ascites: the presence of excess fluid (ascetic fluid) in the peritoneal cavity. It is a common clinical finding with a wide range of causes but develops most frequently due to chronic liver disease or some infections.

Ascomycins: a group of monolactams which include ascomycin (also known as immunomycin or FR-900520 and an FK506 analogue) and its derivatives. They have anti-inflammatory and immunosuppressant actions. Ascomycins inhibit the synthesis of both Th1- and Th2-type cytokines and some of them such as pimecrolimus are being developed for topical treatment of skin diseases such as atopic dermatitis.

Paul C, Graeber M, Stuetz A. Ascomycins: promising agents for the treatment of inflammatory skin diseases. Expert Opin Investig Drugs (2000) 9(1); 69-77

Aspirin: also known as acetylsalicylic acid, a salicylate analgesic, antipyretic and anti-inflammatory compound. It is an irreversible cyclooxygenase inhibitor and prevents the production of prostaglandins and autacoids. It acetylates a serine residue in cyclooxygenase at or near the active site inhibiting its functions.


Ass: a symbol used in pharmacokinetics to denote the amount of drug in the body during a fixed rate infusion and at steady state shown in mg or μmole.

Ass,av: a symbol used in pharmacokinetics to denote the average amount of drug in the body during a dosing interval and at steady state shown in mg or μmole.

Ass,max: a symbol used in pharmacokinetics to denote the maximum amount of drug in the body after administration of a fixed dose and at steady state shown in mg or μmole.

Ass,min: a symbol used in pharmacokinetics to denote the minimum amount of drug in the body after administration of a fixed dose and at steady state shown in mg or μmole.

Ass,t<: a symbol used in pharmacokinetics to denote the amount of drug in the body at time t within a dosing interval at steady state following administration of a fixed dose of drug at a fixed dosing interval shown in mg or μmole.

Association constant: a measure of the likelihood of an interaction between a ligand and its target receptor.

Astringent: also know as a styptic, an agent which causes contraction of tissue, inhibition of secretions and which can control (small amounts of) bleeding.

Ataractic: a drug which has a calming effects on humans or animals but one which does not induce sleep. Also known as a tranquilizer.

ATC codes: the anatomical therapeutic chemical classification of a drug which assigns unique code numbers to drugs to facilitate monitoring of their use on a worldwide scale. These codes are maintained by The World Health organisation and can be found here.

Atenolol: an aryloxypropanolamine-type antihypertensive compound which is a selective β1-adrenoceptor antagonist used clinically to treat hypertension but with wider effects on angina and arrhythmias. It causes arterial smooth muscle dilation.
Kahonen M et al.Enhancement of arterial relaxation by long-term atenolol treatment in spontaneously hypertensive rats. Br J Pharmacol. (1994) 112; 925

ATPase: adenosinetriphosphatase, an enzyme (EC which catalyses the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), a reaction which releases energy to power a multitude of biochemical and physiological action such as pumping ions across cell membranes.

Atractyloside: a diterpenoid glycoside and nephrotoxic compound which induces selective proximal renal tubular necrosis at high doses and apoptosis at lower doses. It has been used to induce experimental nephrotoxicity. It either prevents the export of ATP or the import of substrates across the mitochondrial inner membrane.

Atrial natriuretic peptides (ANP): also known as atrionatriuretic factors and atriopeptin, a group of a polypeptide hormones which are natriuretic and cause vasodilation. Human ANP comprises 28 amino acids and is stored as proANP (which contains 126 amino acids) in membrane-bound granules in atrial cardiocytes. Following stimulation, proANP is cleaved to release the mature ANP which has a half-life of 2.5 minutes but which causes natriuresis, diuresis, vasodilation, suppression of renin actions, suppression of aldosterone actions, suppression of sympathetic activity, suppression of ADH and inhibition of vascular smooth muscle growth.
de Bold AJ et al. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci (1981) 28(1):89-94

Atrial natriuretic peptide receptor: a group of three receptors (ANP-A, ANP-B and ANP-C) for atrial natriuretic peptide and which mediate the vasodilatory effects of this hormone peptide. ANP-A mediates most of the known actions of ANP and brain natriuretic peptide while ANP-B is thought to mediate the action of C-type natriuretic peptide in the central nervous system.

Atropine: also known as DL-hyoscyamine, a naturally occurring racemate (it contains both D and L isomers) of tropane alkaloids (from Atropa belladonna ,the toxic plant deadly nightshade, and hence also known as a belladonna alkaloid). It is a competitive and non-selective muscarinic receptor antagonist which blocks the muscarinic actions of acetylcholine and other parasympathomimetic drugs. It was first isolated in 1831 but has been use in folk medicine for centuries and as an arrow poison since high doses cause death by heart failure. It causes dilation of the pupils, slowing of heart rate, a decrease in gastrointestinal motility and it inhibits the flow of sweat, mucous and saliva. Atropine was once used in surgical premedication to decrease saliva flow but is no longer the drug of choice. It is used, however, used to treat bradycardia following myocardial infarction.
In veterinary pharmacology, atropine is used as a pre-anaesthetic agent to reduce respiratory and salivary secretions. It also has ophthalmological applications to produce cycloplegia and mydriasis and is used to treat renal and biliary colic when used with opioids.

Atropinesterase (AtrE): officially named tropinesterase, a enzyme (EC found in blood which naturally breaks down atropine. Some rabbits, rats and goats possess atropinesterase in their blood and this can make them less susceptible to poisoning by deadly nightshade (which contains atropine).

Atypical antipsychotics: a class of antipsychotic.

: area under the curve

AUCb: a pharmacokinetic symbol used to denote the total area under the blood concentration time curve shown in units of mg-hr/L or M-hr.

AUCm: a pharmacokinetic symbol used to denote the area under plasma metabolite concentration time curve shown in units of mg-hr/L or M-hr.

AUCss: a pharmacokinetic symbol used to denote the area under plasma drug concentration time curve at steady state and within a dosing interval shown in units of mg-hr/L or M-hr.

Audiogenic seizures: a type of seizure.

AUMC: area under the moment curve

Auranofin: a crystalline gold compound having a gold content of about 29% and with anti- inflammatory properties. It is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis in patients who respond poorly to NSAIDs. Auranofin has a diverse pharmacological profile but appears to inhibit the aggregation of macroglobulins and thus inhibit the formation of immune complexes. It has lysosomal enzyme inhibiting actions the release of which has a pro-inflammatory effect.

Autacoids: also referred to a local hormones, short-lived, locally-acting, hormone-like agents which include a very diverse range of molecules such as histamine, bradykinin, nitric oxide, prostaglandins, leukotrienes and serotonin.

Autocrine: relating to self-stimulation by the production of specific factors usually hormones which act upon specific receptors on the cells that produced this factor. The autocrine system in the body usually refers to any cells affected by modulating factors they produce such as the production of cytokines by immune cells and the production and effects of growth factors, cytokines, and chemokines expressed and secreted by normal early and differentiated haematopoietic cells on blood cell development. See also intercrine and paracrine.

Autoimmune: relating to the lack of tolerance to an organism's own tissues where components of the immune system attack and destroy tissues of the same organism that produced them. Examples of autoimmune diseases include multiple sclerosis, ophthalmia sympathica, myasthenia gravis, rheumatic fever and rheumatoid arthritis.

Autoimmune-prone mouse: a mouse strain in which B and T cells are activated and these animals are prone to develop autoimmune disorders. They are used in research into autoimmune diseases and the drugs which modulate them.

Autonomic: relating to the autonomic nervous system, the division of the nervous system which controls the actions of smooth muscle, cardiac muscle and gland cells and comprises opposite-acting sympathetic and parasympathetic parts.

Autopharmacology: the study of the effects of local hormones or autacoids.

Autoradiography: a method to study the distribution of compounds throughout the body following administration of a radiolabelled compound. A radiolabelled compound is administered to an animal then at some time after dosing the animal is sacrificed, frozen then slices of the whole body are prepared. These are then measured for their radioactive emissions by laying them on light- or X-ray- sensitive film to determine the distribution of drug. This highest level of radioactivity indicates the greatest concentration of drug.

Autoreceptors: also known as presynaptic receptors, receptors found associated with a variety of neurotransmitter systems, which are present on transmitter-releasing presynaptic neurones and which control neurotransmitter release via an autoinhibitory feedback mechanism. They can be agonised and antagonised just like postsynaptic receptors to inhibit (presynaptic agonist) or enhance (presynaptic antagonist) transmitter release.
Starke K et al. Modulation of transmitter release by presynaptic autoreceptors. Physiology Review (1989) 69; 864-989Miller RJ. Presynaptic receptors. Ann Rev Pharmacol Toxicol. (1998) 38; 201-227

Auxometry: the measurement of growth.

Auxotonic: occurring against increasing force of muscle contraction.

Axelrod, Julius (1912-2004) : US biochemist and neurologist who shared the Nobel Prize for Physiology or Medicine with Katz and von Euler in 1970 for their discoveries concerning the humoral transmitters in the nerve terminals and the mechanism for their storage, release and inactivation.
http://nobelprize.org/medicine/laureates/1970/axelrod- bio.html. A collection of his work can be found at http://profiles.nlm.nih.gov/HH/

Axenic: not contaminated with microorganisms. A term used in relation to the rearing of animals such as common albino rats and pure cultures of microorganisms.

Axoplasmic flow: the flow of substances such as neurotransmitter-synthesising enzymes along the nerve fibre from the cell body to the synapse. This flow, which plays no part in nerve impulse conduction, is dependent on microtubules and neurofilaments present along the entire length of the neurone. Acetylcholinesterase, for example, is synthesized in the cell body and is transported by axoplasmic flow to the synapse. Axoplasmic flow rates vary according to the type of nerve and the substance being transported but can range from about 1mm/day to about 3m/day.

Azathioprine: a purine analogue which inhibits purine synthesis in cells (it is an antimetabolite) leading to a decrease in clonal proliferation in the induction phase of an immune response so causing immunosuppression (it is an antiproliferative immunosuppressant). It is metabolized to yield mercaptopurine and is used clinically in the suppression of organ transplant rejection usually when steroid therapy is not enough. It is also used to treat rheumatoid arthritis due to its immunosuppressant effects but is not the drug of choice here due to its toxicity. Azathioprine is actually carcinogenic and can cause bladder cancer, leukemia and lymphoma.

Azoles: a family of broad-spectrum antifungal agents originally developed in the late 1960s and which all contain a 5-membered azole ring comprising two (imidazoles) or three (triazoles) nitrogen atoms. They act by inhibiting a cytochrome P450 which catalyzes the 14 α-demethylation of lanosterol to ergosterol (the main sterol in fungal membranes). This leads to accumulation of 14-methylated sterols (and depletion of ergosterol) which induces permeability changes in fungal membranes, membrane leakage, incorrect synthesis of chitin, inhibition of replication and eventually fungal death. Examples of imidazole-type azoles include clotrimazole, miconazole, ketoconazole, fenticonazole and tioconazole and triazoles include fluconazole, itraconazole and terconazole. The diagram shown two typical imidazoles and the azole moiety is shown in blue.

Azoles are effective in the treatment of both topical fungal infections including dermatomycoses such as athletes foot (caused by Tinea pedis), skin ringworm (caused by Tinea corporis) and nail infection (caused by Tinea unguium) and candidiasis such as skin, vaginal and oral thrush (caused by Candida albicans). Azoles are also effective against systemic infections including blastomycoses, coccidiomycoses and sporotrichoses.