DA: Dopamine

Dactinomycin: also known as actinomycin D, a cytotoxic anticancer compound used clinically to treat paediatric cancer. Dactinomycin binds to guanine residues in DNA and blocks the movement of RNA polymerase thus preventing transcription and inhibiting protein synthesis.

DAGO: DAMGO

Dahl salt-sensitive rat: a strain of rat (Dahl strain) which is genetically sensitive to salt and which shows clear hypertension when fed on a high sodium chloride diet.

Dahl salt-resistant rat: a strain of rat (Dahl strain) which is genetically resistant to the hypertensive effects of salt when fed on a high sodium chloride diet.

Dale, Sir Henry H (1875-1968): a British physiologist who shared the 1936 Nobel prize for Physiology or Medicine with Loewi 'for their discoveries relating to chemical transmission of nerve impulses'. In 1906 he showed that the effects of some neurones could be mimicked by some compounds in the parasympathetic nervous system. This was followed by the description of the effects of nicotine. In 1913 Dale showed that adrenaline causes two distinct effects in vascular beds, i.e. vasoconstriction and vasodilation depending on the tissue. Dale also showed that this vasoconstriction could be abolished if an animal was pretreated with an ergot derivative.
http://nobelprize.org/medicine/laureates/1936/dale-bio.html

Dale's principle: a principle put forward by Henry Dale in 1935 which states that a neurone only releases one neurotransmitter. Eccles went on to modify this principle to say that a neurone releases only one transmitter at all its processes. This principle is known not to be true for some neurones which release co-transmitters.

Dalton: a unit of mass equivalent to 1/16th the mass of the oxygen atom or about 1.65 x 10^-24g. The molecular weights of proteins are usually expressed in kilodaltons (kDa).

DAMGO: also known as DAGO, a synthetic enkephalin pentapeptide which is used as a pharmacological tool as it is a highly selective m-opioid receptor agonist.

4-DAMP: an M₃ muscarinic receptor antagonist and a pharmacological tool used in studies of M₃ receptors.

Danazol: an anterior pituitary suppressant ((17a)-Pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol) with weak androgenic effects. It inhibits pituitary gonadotrophins and has anti-androgenic, anti-oestrogenic anti-progestogenic effects. Danazol is used clinically to treat endometriosis and has been used to treat mammary dysplasia and gynaecomastia.

Dantrolene: an imidazolinedione derivative and centrally acting skeletal muscle relaxant used clinically to treat muscle spasm, spasticity and malignant hyperthermia. Dantrolene exhibits fewer central adverse effects than other drugs of its kind. It inhibits Ca²⁺ release from sarcoplasmic reticulum due to inhibition of ryanodine receptor (RYR) channels. Dantrolene shows selectivity for RYR1 and RYR3 over RYR2 receptors and acts and a neuroprotectant since it protects cells against the effects of excitatory amino acids.

Dapropate: an N,N-dimethyl-β-alinate salt. Examples include colforsin daropate used to treat heart failure.

Dapsone: an oral antileprotic drug also used clinically to treat dermatitis herpetiformis. It shows potent antibacterial activity against the causative organism, Mycobacterium leprae, and is used to treat both multibacillary and paucibacillary leprosy. It is structurally related to sulphonamides and probably acts by inhibition of folate synthesis.

Darifenacin: a non-subtype selective muscarinic receptor antagonist. Tritiated darifenacin has been use as probe in the investigation of M₃receptors.

Datura alkaloids: also known as belladona alkaloids, a type of tropane alkaloid obtained from Atropa belladonna and other plants of the genus Solanacea. Examples include atropine and hyoscyamine.

Daunorubicin: an anthracycline antibiotic used clinically to treat acute leukaemia and AIDS-related Kaposi’s sarcoma. It inhibits RNA and DNA synthesis and induces DNA fragmentation.

DBI: diazepam-binding inhibitor

DCVC: S-(1,2-dichlorovinyl)-l-cysteine.

db/db mouse: an animal used as a model of non-insulin-dependent (type II) diabetes mellitus and obesity. It is used in diabetes and obesity research as it closely resembles human obesity.

DBMA: 7,12-dimethylbenz(a)anthracene, a carcinogen and a chemical used experimentally to induce the formation of cancers particularly mammary tumours.

DDC: diethyldithiocarbamate

DDD: defined daily dose, a term used to determine the consumption of specific types of drugs by the population as a whole.


de novo: afresh, from the beginning; a term used to denote the origin of certain biogenic compounds in tissues indicating that they do not naturally circulate around the body in the blood but are newly synthesized when a particular stimulus is received. Examples include prostaglandins and adrenaline.

Debrisoquine: a tetrahydroisoquinoline derivative and an adrenergic neurone blocker which prevents the release of noradrenaline from post-ganglionic adrenergic neurones. It has been used clinically to treat hypertension.

Debrisoquine polymorphism: a genetic abnormality in which debrisoquine is metabolised more slowly than usual due to a defect in the enzyme responsible for detoxifying it.

Decamethonium: a polymethylene bistrimethylammonium salt and a depolarizing skeletal muscle relaxant which acts at neuromuscular junctions where it stimulates (is an agonist of) nicotinic receptors and which has weak antagonist actions at autonomic ganglia. Decamethonium mimics the effects of acetylcholine but is metabolised (hydrolyzed) more slowly than acetylcholine.

Decerebrate: an animal in which cerebral brain function has been abolished by removing the cerebrum, cutting the brain stem or severing certain arteries in the brain stem usually for the purpose of experimentation where CNS function will interfere with peripheral reflexes.

Decongestants: drugs used to reduce congestion in the upper airways and nose. Vasoconstrictors such as sympathomimetic agents are used as decongestants and are usually applied topically partly to help avoid systemic side effects.

Decoy: a substance usually a protein or oligonucleotide which ameliorates the effect of a ligand at its receptor site by binding to the ligand and preventing the ligand binding with its receptor. For example, etanercept is a soluble and dimeric fusion protein which binds to TNF-α and is used to treat rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. It acts by 'mopping up' circulating TNF-α (which is a pro-inflammatory cytokine) making less of it available for binding to its receptor and so ameliorating its effects. Etanercept is actually a soluble form of one of the two known TNF-α receptors (the 75kDa form) which can bind two TNF-α molecules. (See http://www.fda.gov/cder/foi/label/2000/etanimm060600lb.txt). Oligonucleotide decoys are typically synthetic single-stranded oligonucleotides which hybridizes to form a duplex/hairpin with a specific transcription factor to inhibit the expression of a specific protein. They are being investigated for their use in restenosis, vein grafts, myocardial infarction and rheumatoid arthritis.

Defensins: a family of antimicrobial peptides that have been observed in humans, animals and plants. They play an important role in host defenses against infections, inflammation, wound repair and acquired immunity. They are divided into a-defensins and β-defensins according to disulfide pairing of their characteristic six cysteine residues.

Defensive burying behaviour: also referred to as the conditioned defensive burying (CDB) test, a test of anxiety and used in the evaluation of anxiolytics. This test is based on the fact that rodents tend to cover or bury the source of a noxious or aversive stimulus. Compounds with anxiolytic effects tend to abolish defensive burying behaviour. This CDB is a conditioned fear-related response to stimuli such as electrical shock with a probe and results in animals heaping litter or bedding on the source of the stimulus.
Craft RM, Howard JL, Pollard GT. Conditioned defensive burying as a model for identifying anxiolytics. Pharmacol Biochem Behav. 1988, 30(3); 775-80

7-Dehydrocholesterol reductase: also known as delta(7)-dehydrocholesterol reductase, an enzyme (EC 1.3.1.21) which catalyzes the terminal step in cholesterol synthesis, ie reduction of 7-dehydrocholesterol to form cholesterol.

7-Dehydrocholesterol reductase inhibitor: compounds which inhibit 7-dehydrocholesterol reductase and so inhibitors of cholesterol biosynthesis. They have been developed for the treatment of hyperlipidemia. Examples include AY 9944 and BM 15.766.

Dehydropeptidases: a family of enzymes which inactivate some lactam antibiotics such as imipenem. They are located mainly in the kidneys.

Dehydropeptidase inhibitors: compounds which inhibit dehydropeptidases and so potentiate the effects of lactam antibiotics. Examples include cilastin, an inhibitor of renal dehydropeptidase I.

Delta sleep-inducing peptide (DSIP): a circadian-dependent, sleep-inducing nonapeptide present in neurons, peripheral organs, and plasma. It induces mainly delta sleep in mammals and has effects on thermoregulation, heart rate, blood pressure, pain threshold and the lymphokine system.
Schoenenberger G et al. A naturally occurring delta-EEG enhancing nonapeptide in rabbits. X. Final isolation, characterization and activity test. Plügers Arch (1977) 369; 99-109

Deltorphins: endogenous linear heptapeptides isolated originally in 1987 from skin extracts of Amazonian frogs belonging to the genus Phyllomedusa and which have a high affinity and selectivity for d-opioid binding sites. They penetrate the blood-brain barrier when given systemically and have antinociceptive effects.
Lazarus LH, Bryant SD, Cooper PS, Salvadori S. What peptides these deltorphins be. Prog Neurobiol. 1999, 57; 377-420

[D-Ala²]-Deltorphin II: a selective peptide agonist for ä-opioid receptors. It has antinociceptive actions in vivo.
Sanchez-Blazquez P, Garzon J. Delta opioid receptor subtypes activate inositol-signalling pathways in the production of antinociception. J Pharmacol Exp Ther (1998) 285;820

Demulcent: a soothing, usually mucilaginous or oily substance used to relieve pain in inflamed or irritated mucous membranes. Examples include glycerine and lanolin.

Dendrobatid frog: a poisonous South American frog (Dendrobates pumilio) from which certain alkaloid toxins such as pumilotoxins are derived from its skin.

Dendrotoxins: a family of closely related 59 amino acid peptides isolated form the venom of green mamba snakes (Dendroaspis angusticeps and Dendroaspis polylepsis). They comprise three disulphide bonds and exist in several forms, ie α, β₁, β₂, γ and δ. They are neurotoxic and enhance the release of acetylcholine at neuromuscular junction sites causing convulsions. They also block voltage-gated potassium channels.

Denervation supersensitivity: a form of neuronal supersensitivity which follows surgical or chemical denervation. For example, chronic treatment of rats with reserpine for 2 weeks will produce supersensitivity in the contractile response to phenylephrine of isolated rat tail artery and is thought to be due to receptor upregulation.

Denopamine: a selective β₁-adrenoceptor agonist and which has positive inotropic actions.

Denudation: generally, the removal of endothelial cells from blood vessels. This can be achieved by rubbing or gentle scraping and is important in order to remove the effects of chemical mediators released by these cells such as endothelin.

Deoxycorticosterone acetate (DOCA): a potent mineralocorticoid which is used to induce hypertension in experimental animals. Typically, DOCA at a dose of 15 mg/kg is administered subcutaneously twice a week for two weeks to induce marked hypertension which is sustainable when animals are provided NaCl in their drinking water.

Depolarization: a process in which a membrane changes its normal resting polarity to a different state. For example, the usual resting polarization of a nerve membrane is due to the presence of K⁺ ions inside the neuroplasm within the cells and Na⁺ ions outside the membrane. Depolarization occurs when an electrical impulse triggers active transport of Na⁺ ions into the cell and K⁺ ions out of the cell.

Depolarizing block: a form of neuronal block caused by compounds such as succinylcholine and decamethonium which block neuronal transmission by causing prolonged depolarization of the end plate at the neuromuscular junction.

Depot formulation: a formulation which releases the active drug over a period of hours, days, weeks or months from the site (depot) at which it is administered. Typically, drugs for the long-term treatment are given as depot formulations and include chemical contraceptives such as norethisterone enantate which is given as a deep intramuscular oily injection into the gluteal muscle and which provides contraception for about 8 weeks.

Depsipeptide: polypeptides which contain ester (-O-) bonds in addition to peptide bonds. Naturally occurring depsipeptides are very often cyclic and include peptolides, O-peptides and peptide lactones. This latter group include some compounds of pharmacological importance such as antibiotics. Peptide lactone antibiotics include dactinomycin.

Dermorphins: amphibian opiate peptides isolated from the skins of arboreal frogs of the genus Phyllomedusinae. They have higher antinociceptive efficacy and potency than morphine and may be less likely to produce tolerance.
Melchiorri P, Negri L. The dermorphin peptide family. Gen Pharmacol. 1996 27:1099-107

Desensitization: a decrease in response in the continuing presence of a agonist and a term which implies a change in receptor sensitivity. A term often confused with fade and tachyphylaxis.

Desglugastrin: a stimulant of gastric acid secretion used (rarely) as a pharmacological tool.

Designer drug: a drug usually with psychoactive properties synthesized specifically for distribution on the illicit drug market to circumvent regulations concerning controlled substances.

Desipramine: also known as desmethylimipramine and norimipramine, a tricyclic antidepressant and the main active metabolite of imipramine. It inhibits the reuptake of noradrenaline into adrenergic neurones and has antidepressant and sedative actions.

Desmopressin: a vasopressin receptor agonist and synthetic analogue of arginine vasopressin. It is used clinically to treat diabetes insipidus, primary nocturnal enuresis and postoperative polyuria.

DETCA: diethyldithiocarbamic acid

Dexamethasone: a potent steroid with corticosteroid and glucocorticoid actions and with anti-allergic and anti-inflammatory effects. It is used topically in the treatment of skin disorders such as eczema and dermatitis and for congenital adrenal hyperplasia and cerebral oedema.

Dextromethorphan: a centrally acting antitussive compound which increases the cough threshold reflex. Despite being a morphinan, it has very low potential for abuse, is non-analgesic and is a widely used non-opioid antitussive available in many countries OTC.

DFP: diisopropylfluorophosphate

DHFR: dihydrofolate reductase

DHFRI: dihydrofolate reductase inhibitors

Diabetogenic: a substance which can cause diabetes mellitus usually be destroying insulin-producing cells in the pancreas. Examples include alloxan and streptozotocin.

Diacetylmorphine: also known as diamorphine and heroin.

Diacylglycerol (DAG):

Diacylglycerol O-acyltransferase (DGAT): sometimes referred to as acetyl CoA:diacylglycerol O-acyltransferase, two isozymes (DGAT1 and DGAT2) (EC 2.3.1.20) responsible for the formation of triacylglycerol from 1,2-diacylglycerol and acetyl CoA. They are essential enzymes in the final stage of mammalian triglyceride synthesis and are considered to be involved in the development of obesity, insulin resistance, and leptin resistance.

Diacylglycerol O-acyltransferase inhibitors: inhibitors of diacylglycerol O-acyltransferase and compounds which are being developed for the treatment of hyperlipidaemia, obesity and diabetes mellitus. Examples include xanthohumol and amidepsine E.

Diamine oxidase (DAO): an enzyme (EC 1.4.3.6) officially known as amine oxidase and also known as histaminase which is the main histamine degrading enzyme (but also acts on putrescine and cadaverine). It forms the inactive metabolite imidazolylacetic acid via an intermediate aldehyde and is present mainly in the intestinal mucosa and kidneys. Deficiency of this enzyme leads to histamine intolerance typified by a reaction to histamine in foods which appears as chronic headache, diarrhoea, vomiting, flush, urticaria, asthma-like symptoms and rhinitis.

Diamine oxidase inhibitors: inhibitors of diamine oxidase and so inhibitors of histamine detoxification. Examples include aminoguanidine (also known as guanylhydrazine and used in the inhibition of formation of advanced glycation end products (AGE) in the treatment of diabetic complications such as nephropathy), some amiloride analogues, metronidazole and the alkaloid nazlinin.

2,4-Diaminopyrimidines: a class of synthetic antibacterial compounds which include tetroxoprim and trimethoprim (which both act as folate antagonists). The 2,4-diaminopyrimidine moiety is shown in blue.

Diamorphine: also known diacetylmorphine and heroin.

Diaphoretic: a substance which induces diaphoresis (sweating).

Diarylsulphones: a class of non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors. This class of antivirals includes 2-nitrophenyl phenyl sulphone. The diarylsulfone moiety is shown in blue in the figure.
McMahon JB et al. Diarylsulfones, a new chemical class of nonnucleoside antiviral inhibitors of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother (1993) 37(4);754-60



Diastereoisomer: a stereoisomer of a compound which has two or more chiral centers but which is not a mirror image of another stereoisomer of the same compound.

Diazepam: also known as valium, one of the oldest benzodiazapines (7-chloro-1,3-dihydro-1-methyl-5-2H-1,4-benzodiazepin-2-one) which has been used as an anxiolytic, sedative hypnotic, anticonvulsant, antiepileptic and muscle relaxant. It acts by interacting with GABA_A receptors.

Diazepam-binding inhibitor (DBI): an endogenous neuropeptide showing high affinity to mitochondrial DBI receptors (it is a natural ligand for these receptors) and also located on extraneuronal glial cells. This neuropeptide binds to (the same sites as benzodiazepines) and modulates the actions of neuronal GABA_A receptors by allosteric modification and acts as a negative modulator of the GABA_A receptor and so decrease in the binding of GABA to these receptors. It is known to acts as a benzodiazepine inverse agonist (it binds to benzodiazepine binding sites but shows opposite effects to them, ie increases anxiety).

Diazepam-binding inhibitor antagonists:

Dibenzazepines: a class of classical antipsychotics. Examples include clothiapine, loxapine and clozapine which is used clinically to treat schizophrenia including psychoses in Parkinson’s disease in patients unresponsive to conventional antipsychotic drugs. The dibenzazepine moiety is shown in blue.



Diclofenac: a nonsteroidal anti-inflammatory drug (NSAID) used clinically to treat pain and inflammation in rheumatic disease, acute gout, postoperative pain and other musculoskeletal disorders. Diclofenac is a non-selective COX inhibitor and so decreases the production of prostaglandins and thromboxanes.

S-(1,2-dichlorovinyl)-l-cysteine (DCVC): a cataractogenic neurotoxin.

Dicoumarol: also known as 3,3’-methylenebis(4-hydroxycoumarin), an anticoagulant and vitamin K antagonist which causes hypothrombinaemia in many species of animals because in inhibits the action of vitamin K which is essential in blood coagulation.

Didanosine: a nucleoside reverse transcriptase inhibitor used clinically in the treatment of HIV infections in combination with other antivirals.

Dietary obese animals: animals which are not genetically susceptible to obesity but which have become so due to the amount and type of feed they have consumed.

Diethyldithiocarbamate (DDC): a compound used to induce experimental antral ulcer in animals. DDC is a superoxide dismutase inhibitor and a dopamine β-hydroxylase inhibitor.

Diethyldithiocarbamic acid (DETCA): an inhibitor of Cu/Zn superoxide dismutase and a copper chelator.

Diethylstilbestrol: also known as stilboestrol, a synthetic, nonsteroidal estrogen which has been used clinically to treat prostate cancer and breast cancer in menopausal women but is not a drug of choice due to its side effects.

Digestives: also known as digestants, agents used to facilitate digestion by a variety of mechanisms.
- Stomachics include bitter substances such as quinine, gentian and strychnine which were thought to improve gastric function possibly by a local reflex action on the gut. Quinine and gentian are common components of tonics and cocktails.
- Digestives were thought to aid digestion and included hydrochloric acid, pancreatin and pepsin although all of these were of dubious value in aiding digestion.
- Carminatives such as mild irritants and volatile oils were assumed to increase peristalsis and thus reduce the distended feeling following overeating. Examples of carminatives include after-dinner mints, chewing gum and liqueurs which are still popular.
- Intestinal absorption inhibitors include sodium phytate (a Ca and Mg ion absorption inhibitor), cholestyramine (inhibitor of bile acid absorption) and acarbose (an inhibitor of intestinal carbohydrate breakdown).

Digoxin: a cardiac glycoside used clinically in the treatment of heart failure and supraventricular arrhythmias.

Digitalis: also known as foxglove, purple foxglove, digifortis and digitora, and the name given to group of cardioactive compounds from the dried leaves of the plant Digitalis purpurea and Digitalis lanata. Digitalis glycosides which include digitoxin have cardiotonic actions and are used clinically in the treatment of chronic heart disease. The alkaloids obtained from leaves of plants of the genus Digitalis are known as digitalis alkaloids and include ouabain, digoxin and digitoxin and the latter two are used clinically to treat heart failure and supraventricular arrhythmias.

Digitalis alkaloids: alkaloids obtained from the leaves of plants of the genus Digitalis including Digitalis purpurea (purple foxglove) and Digitalis lanata (woolly foxglove). The 3 most important alkaloids are digitoxin, digoxin and gitoxin.

Digitanols: a group of plant glycosides which occur together with cardiac glycosides but which have no cardiotonic activity.

Digitonin: a mixture of four different steroid saponins obtained from the seeds of the purple foxglove (Digitalis purpurea).

Digitoxin: an alkaloid obtained from digitalis. It has cardiotonic effects, eg increases the force of heart muscle contraction, it slows the heart and reduces the rate of contraction through the AV node and can block AV conduction and increase ectopic pacemaker activity. It acts by increase in vagal activity in the heart (the vagus nerve has parasympathetic actions on the heart and slows its rate) and by inhibiting the Na⁺/K⁺ pump by binding to the extracellular domain of the a-subunit of Na⁺/K⁺ ATPase on myocytes. This inhibition of Na⁺/K⁺ ATPase causes an increase in Na⁺ and slows the efflux of Ca²⁺ since efflux of Ca²⁺ is Na⁺/Ca²⁺ exchange dependent. Increased Ca²⁺ is store in the sarcoplasmic reticulum and this increases the amount released by each action potential.

Digoxin: a cardiac glycoside used clinically to treat heart failure and supraventricular arrhythmias. It has the same mechanism of action as digitoxin.



Dihydrofolate reductase (DHFR): an enzyme (EC 1.5.1.3) in thymidine synthesis which catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate and the conversion of folate to tetrahydrofolate (at a lower rate). Tetrahydrofolate is an essential cofactor in the conversion of deoxyuridylate to deoxythymidylate by thymidylate synthetase so DHFR is an essential enzyme in DNA synthesis.

Dihydrofolate reductase inhibitors (DHFRI): inhibitors of dihydrofolate reductase and so compounds which inhibit DNA synthesis. These compounds form a class of anticancer agents referred to as folate antagonists and as antimetabolites which inhibit dihydrofolate reductase by substrate competition and include methotrexate (formerly known as amethopterin) which binds irreversibly to dihydrofolate reductase and so inhibits cell division.

Dihydroorotate dehydrogenase (DHODH): an enzyme (EC 1.3.99.11) which is essential in pyrimidine synthesis (it oxidizes dihydroorotate to orotate) and so is essential in DNA synthesis.

Dihydroorotate dehydrogenase inhibitors (DHODHI): compounds which inhibit dihydroorotate dehydrogenase and so inhibitors of DNA synthesis. Examples include the immunomodulatory drug leflunomide. DHODH inhibitors are being developed for the treatment of malaria.

Dihydropyridines: one of three main classes of calcium channel blockers with antihypertensive and anti-angina actions which includes nifedipine, nicardipine, amlodipine, israpidine, felodipine, nimodipine and nisoldipine. The dihydropyridine moiety is shown in blue.



Diisopropylfluorophosphate (DFP): a potent acetylcholinesterase inhibitor and pharmacological tool. It has been used in the treatment of glaucoma.

Dilazep: an adenosine uptake inhibitor which has coronary and cerebral vasodilating effects, platelet aggregation inhibiting actions and inhibits the membrane transport of nucleosides.

Diltiazem: a benzothiazepine-type calcium antagonist which mainly affects heart and smooth muscle to cause vasodilation and coronary artery dilation. It also has an antiarrhythmic action and is used clinically in the prophylaxis and treatment of angina and in the treatment of hypertension.

Dimethylnitrosamine (DMN): a carcinogen present in tobacco smoke and some foods and a compound used to induce experimental liver damage in animals.

Dimethylphenylpiperazinium (DMPP): a selective nicotinic agonist which has been used as a research tool to investigate nicotinic receptors. DMPP activates nicotinic receptors in autonomic ganglia but has little effect on nicotinic receptors at the neuromuscular junction.

Dimethylsulphoxide (dimethylsulfoxide, DMSO): a solvent commonly used in pharmacology to solubilized drugs. It also facilitates toxicants, drugs and allergens to penetrate the skin more readily. It is quite toxic and prolonged exposure can cause a wide variety of disorders including chemical pneumonia, renal toxicity, headache and diarrhoea. It has some anti-inflammatory effects and exhibits mild cholinesterase inhibition and vasodilation. DMSO is used in veterinary pharmacology as a topical anti-inflammatory particularly to reduce swelling due to musculoskeletal trauma. It traps free radicals such as superoxide. DMSO is also used as varnish and paint remover, hydraulic fluid and as an antifreeze!

N-(4,4-di-(3-methylthien-2-yl)but-3-enyl) nipecotic acid: a potent and specific GABA uptake blocker. (R)-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl) nipecotic acid hydrochloride is also known as tiagabine and is used as an antiepileptic drug.

Dinoflagellate toxins: toxins obtained from marine dinoflagellates, the majority of which are plankton. These can live freely in the sea (where they sometimes cause 'red tide') or can be present in fish, shellfish and other animals that consume them. These toxins, which include brevetoxins, ciguatoxins and saxitoxin (the most common dinoflagellate toxin) cause paralysis and sometimes death in humans that ingest them from contaminated seafood due to paralysis of the lungs or heart failure. They account for the vast majority of cases of seafood poisoning. Another example of a dinoflagellate toxin is okadaic acid, a polyether fatty acid, an ionophore and tumor promoter which potently inhibits serine threonine specific protein phosphatases 1 and 2A.

Dinoprostone: a prostaglandin derivative used clinically to induce labour (it is an oxytocic) and usually applied as a vaginal tablet. It is one of the most common and most biologically active mammalian prostaglandins.

Dinitrofluorobenzene (DNFB): a compound used to induce inflammation of the skin in the investigation of the effects anti-inflammatory compounds using passive cutaneous anaphylaxis as a model of inflammation.

Dipeptidyldipeptidases: a family of proteases about 10 of which are known. They are often referred to by other names such as dipeptidyl peptidase I is cathepsin C.

Diphenylbutylpiperidines: a class of atypical antipsychotics which are structurally related to the butyrophenones such as haloperidol. Examples include pimozide, penfluridol and fluspirelene. Pimozide is a D₂ dopamine antagonist and is used clinically to treat schizophrenia, monosymptomatic hypochondriacal psychosis and paranoid psychosis.

Diphenylhydramine: a histamine antagonist (2-(diphenylmethoxy)-N,N-dimethylethylamine) which has been used to treat allergic rhinitis and dermatitis, as an anti-emetic in motion sickness and is used clinically as a sedative in over-the-counter remedies for sleep disturbances. It is an H₁-receptor antagonist which exhibits significant antimuscarinic effects and local anaesthetic activity.

Dipsogen: an agent which stimulates drinking (of water). Dipsogenic hormones include relaxin and angiotensin II.

Dipsogenic receptors: receptors which regulate the intake of water. Dipsogenic receptors sensitive to angiotensin II are present in the subfornical organ.

Dipyridamole: a coronary vasodilator, adenosine transport inhibitor and phosphodiesterase inhibitor. It is used clinically as an adjunct to treatment with oral anticoagulants for the prophylaxis of thromboembolism associated with prosthetic heart valves.

Direct-acting carcinogen: a carcinogen which acts without metabolic conversion from its inactive form to cause cancer unlike procarcinogens which need to undergo metabolic activation to be cancer forming.

Directly acting cholinoceptor stimulants: cholinergics

Discontinuation syndromes: disorders caused by the abrupt cessation of administration of drugs such as selective serotonin reuptake inhibitors (SSRI) and  other neuroleptics. Symptoms of discontinuation syndrome include headaches, anxiety, restlessness, dystonia and irritability.

Disintegrant: a substance added to a tablet or capsule to facilitate its disintegration once it reaches the stomach or small intestines. Examples include resins such as Amberlite which swell when they get wet. Other examples of disintegrants include croscarmellose sodium, crospovidone and sodium starch glycolate.

Disintegrins: a family of cysteine-rich peptides of about 70 amino acid residues obtained from snake venom. Disintegrins contain the arginine-glycine-aspartic acid (RGD) sequence and this sequence binds to integrin receptors on cell surfaces such as platelet and lymphocytes and competitively inhibits normal integrin-ligand interactions (essential for cell adhesion). Disintegrins thus block adhesive functions and act as platelet aggregation inhibitors, cell to extracellular matrix adhesion inhibitors and some have antitumour and anti-metastasis activity. Examples include contortrostatin, jarastatin, kistrin, flavoridin and echistatin.

Disease-modifying antirheumatic drugs (DMARD): antirheumatic compounds which are not steroids and are not NSAIDS. They are often used as second-line therapy in patients who show active rheumatoid arthritis despite treatment with NSAIDs or steroids. DMARDs include methotrexate, sulfasalazine, hydroxychloroquine, gold compounds such as auranofin, azathioprine, D-penicillamine and cyclosporine. DMARDs have the potential to reduce or prevent joint damage and to preserve joint integrity and function.

Dissociation constant (Kd): an indication of the ability of a large unit to (reversibly) break apart to form smaller units. The dissociation constant is important in pharmacology as is gives an indication of how strongly a ligand binds to a receptor (which is strictly speaking measured by the association constant). Drugs should ideally have low dissociation constants, ie they bind tightly to their receptors at low concentration. A high concentration of ligand required to form the ligand-receptor complex indicates that the strength of binding between them is low and the Kd would therefore be higher (mM range rather than nM range) because more ligand ir required to form the ligand-receptor complex.

Dissociative anesthesia: a form of anesthesia.

Distomer: the less therapeutically potent molecule in an enantiomeric pair. The opposite is eutomer.

Disulfiram: also known as Antabuse, a compound used to treat chronic alcohol dependence. Disulfiram gives rise to unpleasant side effects even after the consumption of small amounts of alcohol and it causes the accumulation of acetaldehyde in the body because in inhibits aldehyde dehydrogenase.

Diuretics: compounds which increases the formation of urine. They are used clinically in the treatment of hypertension and act via a variety of mechanisms. They include carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics (high-ceiling diuretics), thiazide diuretics and potassium-sparing diuretics.

Diuresis: a process of increased urine formation.

Dizocilpine: also known as MK-801, a potent and selective non-competitive NMDA receptor antagonist. It acts by binding to a site located within the NMDA-associated ion channel and prevents Ca²⁺ influx. It has anti-ischaemic actions.

D_L: loading dose of a drug usually given in units of mg or μmole.

D_M: maintenance dose of a drug in a fixed-dose dosing regime usually given in units of mg or μmole

DMARD: disease-modifying antirheumatic drug

DNFB: dinitrofluorobenzene, an inflammatory compound used to induce skin inflammation.

DMN: dimethylnitrosamine

DMPP: dimethylphenylpiperazinium

DMSO: dimethylsulphoxide

DMT: N,N-dimethyltryptamine, a hallucinogen and component of Ayahuasca which is a hallucinogenic beverage used in ethnomedicine and shamanism of indigenous Amazonian tribes.

DNA gyrase: also known officially as DNA topoisomerase (ATP-hydrolyzing) and more commonly as topoisomerase II, an enzyme (EC 5.99.1.3) which interconverts isomers of circular double-stranded DNA by altering the degree of its supercoiling, a factor controlling cell division.

DNA gyrase inhibitors: compounds which inhibit DNA gyrase. Examples fall roughly into three classes; coumarins such as coumermycin A, quinolones such as ciprofloxacin and oxolinic acid and 2-pyridones such as ABT-719. DNA gyrase inhibitors have antibacterial actions.

DNA polymerase: officially known as DNA-directed DNA polymerase, an enzyme (EC 2.7.7.7) which elongated DNA chains. It does so by forming a phosphodiester bond between the 5´a-phosphate of one deoxyribonucleotide and the 3´-hydroxyl of another. It cannot initiate DNA synthesis de novo but adds deoxynucleotides one at a time to the 3´ hydroxyl terminus of a preexisting DNA or RNA strand which is known as a primer. DNA polymerase is an essential enzyme in cell replication and several families are known.

DNA polymerase inhibitors: compounds which inhibit the actions of DNA polymerase and so inhibit the elongation of DNA during cell division. They are used as anticancer and antiviral drugs. Examples of antiviral DNA polymerase inhibitors include aciclovir, ganciclovir and foscarnet. These compounds are effective in treating cytomegalovirus infections and (aciclovir and ganciclovir) act by being triphosphated and competing with usual DNA polymerase substrates for incorporation into viral DNA. Foscarnet is a synthetic non-nucleoside analogue of pyrophosphate and acts by binding directly to the pyrophosphate binding site in DNA polymerase. Examples of anticancer polymerase inhibitors include cytarabine, which is an analogue of 2'-deoxycytidine and rifamycin and its derivatives. The structural similarities between guanosine, aciclovir and ganciclovir are shown in the diagram below.



Dobutamine: a synthetic analogue of dopamine and a cardiac stimulant which acts on β₁-adrenoceptors in the heart. It increases heart contractility with little effect on rate and is used clinically for inotropic support in infarction, cardiac surgery, cardiomyopathies, septic shock and cardiogenic shock.

DOCA: Deoxycorticosterone acetate

Docking study: molecular modeling studies which attempt to determine the most appropriate fit between ligands and their binding sites.

Doluisio technique: an in situ perfusion technique using a piece of isolated gut into which the test drug is injected into the lumen to determine the kinetics of drug absorption through the intestines.
Doluisio J et al. Drug absorption. I. An in situ rat gut technique yielding realistic absorption rates. J Pharm Sci (1969) 58(10); 1196-1200

Domagk, Gerhard JP (1895-1964): German physician and physiologist who won the 1936 Nobel Prize for Physiology or Medicine "for the discovery of the antibacterial effects of prontosil".
http://nobelprize.org/medicine/laureates/1939/domagk-bio.html

Domoic acid: an excitatory amino acid and structural analogue of kainic acid which may be more selective than kainic acid at kainite receptor sites. It is obtained from the red alga Chondria armata and has been shown to be responsible for certain incidences of shellfish poisoning notably following the ingestion of mussels.

Domperidone: a benzimidazole D₂ dopamine receptor antagonist which acts in the chemoreceptor trigger zone and is used clinically in the treatment of nausea and vomiting particularly associated with the use of cytotoxic (anticancer) drugs.

Donepezil: a highly selective, long-acting acetylcholinesterase inhibitor used clinically in the treatment of Alzheimer's disease. It increases the levels of acetylcholine in the brain of patients with Alzheimer's disease and appears to correct ACh dysfunction associated with loss of cells in the basal forebrain.
Whitehouse PJ. Donepezil. Drugs Today (Barc) (1998) 34(4); 321-6

DOPA: an aromatic amino acid which is the hydroxylation product of the dietary amino acid tyrosine and which is decarboxylated to form dopamine.

L-DOPA: also known as levodopa, the precursor (3,4-dihydroxyphenylalanine) of dopamine and itself formed by the hydroxylation of tyrosine.

Dopa decarboxylase: officially known as aromatic-L-amino-acid decarboxylase, an enzyme (EC 4.1.1.28) which catalyzes the decarboxylation of DOPA to form dopamine. (See entry under Adrenaline for pathway.)

Dopa decarboxylase inhibitor: a compound which inhibits dopa decarboxylase and so potentiates the effects of dopamine at dopamine receptor sites. Examples include 3-hydroxybenzyl hydrazine (NSD-1015) which is used to study the neurotransmitter-like actions of L-DOPA. Peripheral dopa decarboxylase inhibitor include carbidopa or benserazide and are used in conjunction with L-dopa to treat Parkinson's disease.

Dopamine (DA): a small-molecule neurotransmitter and monoamine involved in the control of both motor and emotional behaviour but found in a relatively small number of brain cells despite its multiple functions. Dopaminergic neurones are found grouped into four major tracts in the brain; the nigrostriatal tract (involved in fine movement), the tuberoinfundibular tract (involved in the control of hormones) and two tracts within the mesolimbocortical system (involved in emotional behaviour).

Dopamine theory of schizophrenia: a theory proposed in 1963 by Arvid Carlsson (who received the Nobel Prize for Physiology or Medicine in 2000) and M Lindqvist in which states that schizophrenia is caused by an overactive dopamine system in the brain because schizophrenia is associated with increased activity at dopaminergic receptor sites. There are arguments for and against this theory. They reported that neuroleptics such as chlorpromazine increase dopamine and noradrenaline turnover in rat brain and postulated that this effect is caused by blockade of catecholamine receptors. The original paper upon which this theory is based is;
Carlsson A, Lindquist M. Effect of chlorpromazine or haloperidol on formation of 3-methoxythyramine and normethanephrine in mouse brain. Acta Pharmacol Toxicol. (1963) 20; 140-144

Dopamine β-hydroxylase: officially known as dopamine-β-monooxygenase, a mono-oxygenase enzyme (EC 1.14.17.1) which catalyzes the conversion of dopamine to noradrenaline. It requires ascorbic acid as a co-factor. (See entry under Adrenaline for pathway.)

Dopamine receptors: receptors for the neurotransmitter dopamine of which five have been characterized by molecular studies. They are classified as D1-like and D2-like receptors. D1-like receptors include D1 and D5 receptors while D2-like receptors include D2, D3 and D4 receptors. They are widely present in the brain with D4 receptors also present in the cardiovascular system.
http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1282

Dopamine receptor agonist: compounds which stimulate dopamine receptors and which are used clinically in the treatment of Parkinson’s disease. Examples of dopamine agonists include apomorphine (non-subtype selective), carmoxirole (peripheral D₂-selective), dihydroergocristine (also a 5-HT antagonist and a adrenergic agonist), piribedil (may be D₃-selective), quinpirole (D₂-selective) and roxindole. Examples of dopamine agonists used in Parkinson’s disease include bromocriptine, cabergoline, lisuride, pergolide, pramipexole and ropinirole.

Dopamine receptor antagonist: compounds which block the effects of dopamine at its receptor sites. Examples include AJ-76 (preferential action at D₂-like presynaptic autoreceptors), amisulpride (selective for D₂/D₃ receptors and an atypical antipsychotic/antischizophrenic drug), clozapine, domperidone (peripheral D₂-like antagonist), eticlopride, haloperidol and pimozide. Dopamine antagonists are used clinically to treat emesis (haloperidol and droperidol), to treat psychoses (haloperidol and clozapine) and to stimulate gastric emptying in the treatment of non-ulcer dyspepsia (domperidone).

Dopamine-releasing drugs: compounds which cause the direct or indirect release of dopamine from dopaminergic neurons. Indirect dopamine releasers include amantidine which is used clinically to treat viral infections (herpes zoster and influenza A) and Parkinson’s disease (where it appears to cause the release if dopamine from intact nerve terminals in the nigrostriatum). Indirectly acting dopamine releasers include glutamate antagonists such as memantine, dizolcipine and riluzole which reduce the activity of glutaminergic fibres projecting into the striatum from the neocortex. Antagonist of this excitatory amino acid transmitter causes disinhibition of nigrostriatal neurones via gabaergic neurons and the consequent release of dopamine in the striatum.

Dopamine reuptake inhibitors (DARI): compounds which prevent dopamine being reuptaken by presynaptic receptors by inhibiting the actions of a dopamine transporter and so compounds which enhance the actions of dopamine on post-synaptic neurones. Examples include amineptine, tetrabenazine, indatraline, BTCP maleate, phenmetrazine and bupropion (used clinically to treat drug addiction).

Dopamine transporter: a sodium-dependent reuptake carrier located in the presynaptic membrane and which removes dopamine from the synaptic cleft and reuptakes it into presynaptic nerves thereby helping to terminate its effects. It is a 12 transmembrane domain transporter with the N- and C-terminal regions located within the cytoplasm and is thought to play an important role in such neurological and psychiatric disorders as Parkinson's disease, Tourette's disease, schizophrenia and drug addiction. DAT is the principal site of action of psychostimulant drugs such as cocaine and amphetamines which both inhibit the activity of this transporter.
Izenwasser S. The role of the dopamine transporter in cocaine abuse. Neurotox Res. (2004) 6:379-83

Dopamine transport inhibitors: compounds which inhibit the dopamine transporter and which increase the levels of dopamine at postsynaptic receptor sites. Examples include GBR 12909, cocaine and amphetamine.

Dopaminergic: relating to the synthesis, storage and release of dopamine.

Dorsal air sac method: a method to investigate the actions of angiogenesis inhibitors and tumour-induced angiogenesis. In this method an air sac is created on the back of an animal such as a rat and the extent of angiogenesis is determined, for example, measuring the accumulation of radioactivity in the air sac after the injection of radioisotope-labeled red blood cells.

Dorsomedial nucleus (DMN)-ablated rat: rats with lesions in the dorsomedial nucleus, a nucleus in the hypothalamus involved in metabolism. Ablation of the DMN in weanling rat leads to a smaller animal with normal glucose and lipid metabolism but with decreased body fat for its size.

Dose dumping: a sudden release of drug from a tablet in the gut due to rupture of a capsule membrane or breakdown of a sustained release system or a sudden increase in blood concentration of a drug as tablet transit in the gut is impaired by the presence of food. Drug delivery systems are designed to avoid dose dumping which can cause very unpleasant adverse effects.

Dose-response curve: also known as concentration-response curve, a graphical representation of the relationship between the concentration or dose of a drug and the response it ellicits. The X-axis shows concentration of a drug on a normal or logarithmic scale and the Y-axis shows the response which could be change in enzyme activity, accumulation of an intracellular second messenger, membrane potential and heart rate. The dose-response curve can provide important information about responses to drugs such as if the drug is acting as a full or partial agonist and help calculate IC₅₀ and ED₅₀ values.

Double blind: also known as double masked, a form of blind test.

Double prodrug: also known as a pro-prodrug, a biologically inactive prodrug molecule which is converted to its active form by two metabolic steps, ie its immediate precursor is as inactive as the form in which it was given.

Down-regulation: a decrease in the number of receptors expressed by an effector cell thereby decreasing its sensitivity to agonist. Down-regulation may be rapid of slow in onset and may be due to receptor internalization.

Doxazosin: a selective α₁-adrenoceptor antagonist used clinically to treat hypertension and benign prostatic hyperplasia. Doxazosin is a smooth muscle relaxant and vasodilator which causes a fall in arterial pressure. It is also used to increase urinary flow in patients with urinary retension. Structurally it is a quinazoline.

Doxepin: a dibenzoxepin tricyclic antidepressant used clinically to treat depressive illness particularly where sedation is required and which is also used to treat pruritis in eczema. Doxepin is also a highly potent H₁ histamine receptor antagonist and binds to H₄ histamine receptors.

Doxorubicin: also formerly known as adriamycin, an anthracycline cytotoxic antibiotic widely used clinically to treat acute leukaemias, lymphomas, solid tumours and some papillary tumors. Doxorubicin has a broad spectrum of action against tumours and intercalates between base pairs in the DNA double helix which inhibits DNA replication and can cause single-stranded DNA breaks.

DPCPX: 1,3-dipropyl-8-cyclopentylxanthine, a potent and selective antagonist for A₁ adenosine receptors. This can be used in adenosine receptor binding studies in tritiated form.

DPPH: 1,1-diphenyl, 2-picryl hydrazyl, a stable radical and one used to test the effects of free radical scavengers.

Drench: a method of administering drugs to animals which involves the direct injection of a drug solution into the mouth cavity of animals such as cattle and sheep. Drench is typically used when treating a large number of animals with drugs such as ivermectin for the treatment of internal and external parasites such heartworm and lice. Drench volumes are typically 10mL/100kg body weight.

Dromotropic: affecting the velocity of conduction of excitation of nerve or cardiac muscle fibres or of atrioventricular conduction. Positive dromotropics, for example, increase cardiac output. Examples include β₁-adrenoceptor agonists.

Drug delivery system (DDS): methods, devices and compounds used in combination with active drugs for the administration of these drugs to specific tissues targets at controlled points or periods in time. DDS include time-release medications, controlled-release agents and percutaneous preparations.

Drug disposition tolerance: a process in which a drug or compound induces its own metabolism to the extent that a greater amount has to be taken to maintain its effects. An extremely good example of this is the consumption of alcohol. This compound enhances its own metabolism by enzyme induction so that individuals  consuming large quantities on a regular basis become somewhat tolerant to the effects of amounts which would get infrequent drinkers drunk.

Drug discovery: the process of discovering drugs from a variety of natural and synthetic sources and testing their suitability for human therapy.
Kaul PN. Drug discovery: Past, present and future. Progress in Drug Research. 1998. 50; 9-105

Drug interaction: a process in which a drug shows an altered response, due to the presence of another drug or other drugs in the body. There are three basic kinds of interaction; pharmacokinetic, pharmacodynamic and pharmaceutic.
- Pharmacokinetic interactions are those in which the presence of one drug alters the absorption, distribution, metabolism and/or excretion of another. For example, drugs which increase gastric motility such as metoclopramide increase the delivery of drugs to the small intestine and increase their rate of absorption, drugs which delay gastric emptying such as anticholinergics decrease the rate of intestinal absorption and tetracyclines chelate cations such as calcium and magnesium to form insoluble complexes and so should not be given with milk of magnesium-containing antacids.
- Pharmacodynamic interactions are those in which the presence of one drug alters the actions of another on specific tissues. For example, antihistamines often have weak anticholinergic actions which reduce the effects of miotics in glaucoma and phenothiazine tranquilizers have α-adrenergic antagonist actions which nullify the vasopressive effect of adrenaline and so can lead to hypotension by allowing adrenaline to exert β-adrenergic actions (this is adrenaline reversal).
- Pharmaceutic interactions are those in which two or more drugs are physically or chemically incompatible and such incompatibility can lead to increase toxicity or drug inactivation. For example, amphotericin B forms a precipitate in an electrolyte solution and ampicillin and furosemide are inactivated in acidic media.
See the RxList (http://www.rxlist.com/) or
Drug Digest (http://www.drugdigest.org/DD/Interaction/ChooseDrugs/1,4109,,00.html) for more specific details.

Drug latentiation: a process in which a biologically active compound is chemically modified to form a new compound which will liberate the parent compound in vivo.

Drug master file (DMF): a regulatory term given to the documents presented by a drug company voluntarily to licensing authorities.

Dual action drug: a drug with two mechanisms of action. Examples include the antidepressant duloxetine which inhibits the reuptake of both 5-HT and noradrenaline in the brain thereby potentiating the effects of both to cause mood elevation. Another example is the antihypertensive omapatrilat, a vasopeptidase inhibitor having dual inhibitory action on angiotensin-converting enzyme and neutral endopeptidase (preventing the breakdown of atrial peptides and bradykinin).

Dualist: a drug with two mechanisms of action. Examples include tramadol which has weak μ opioid receptor agonist actions and inhibits the reuptake of serotonin and noradrenaline. Tezosentan, a dual-action ET-1 receptor antagonist, blocks both ET(A) and ET(B) receptors.

Dunkin-Hartley guinea pig: a common albino outbred guinea pig of the English (short-haired) breed. This strain undergoes spontaneous cartilage degeneration and has been used as a convenient small animal model to study osteoarthritis (OA).

Dunnett’s test: a statistical test used as a specialized multiple comparison test which allows a comparison between a single control group with all other test groups or can be applied to a comparison of effects at time 0 and effects at all other time points. Typically, there are three or more sample populations and differences in the means of two or more test groups can be compared to a reference group.

Dyflos: also known as diisopropylfluorophosphonate or DFP, an organophosphorus anticholinesterase developed before the Second World War as a gas which could be use in chemical warfare. Dyflos inhibits both pseudo- and true cholinesterase thereby potentiating the effects of acetylcholine at neuromuscular junctions and causing muscular paralysis.

Dynorphins: one of three main classes of endogenous opioid peptides and includes dynorphins A and B and fragments of these peptides which are found throughout the central and peripheral nervous systems. Dynorphins are kappa-opioid receptor agonists and are involved in anti-nociception and neuroendocrine signaling.