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 α_1A-adrenoceptor agonist.
Knepper SM et al. A-61603, a potent α₁-adrenergic receptor agonist, selective for the α_1A 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 CCK_A 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. α₁-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 calcitonin_8-32, 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  a₁-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 6.4.1.2) 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.



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 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 deformylases and, 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 2.3.1.26) 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

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 3.5.4.4) 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 2.7.1.20) 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, A_2A, A_2B, 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.
 

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 4.6.1.1) 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.



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.
The summary below shows agonists and antagonists acting on the adrenoceptors in the autonomic nervous system, their receptor subtype preference, if any, and principal physiological action where stimulation of these receptors cause the listed response. The asterisk next to a drug name denotes a selective or largely selective agonist or antagonist.

 

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 ìmole.

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.

Ae_r,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 K_i value.

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, ìμ-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 1.1.1.2) and aldehyde reductase (EC 1.1.1.21). 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 1.1.1.21) 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 3.1.3.1) 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 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.



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.

A_min: 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 3.4.11.2), 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.

A_N,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.

A_N,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 á2 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 3.4.15.1) 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 GABA_B 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