Baboon : a species of mammal used in experiments because they are biochemically, genetically and physiologically similar to humans and some strains show close parallels to human disease processes. Examples include the Senegalese baboon (Papio papio) which are used for the study of photosensitive epilepsy because they shown natural photosensitive epilepsy very similar to that observed in humans. Sacred baboons (Papio hamadryas) also known as the hamadryas baboons which have been used in the investigation of hepatitis and other microbial diseases. Other species used to investigate sleep include Kenya or yellow baboon (Papio cynocephalus) and olive baboon (Papio anubis).

Bacimethrin: a naturally occurring thiamine antimetabolite and antibiotic produced by Bacillus megatherium which is active against some bacterial and yeasts.
Reddick JJ et al. The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite. Bioorg Med Chem Lett (2001) 11(17);2245-8

Bacitracins: branched, cyclic peptide antibiotics produced by various strains of Bacillus sp. and effective against gram-positive bacteria. They inhibit murein synthesis. Bacitracin, which is a mixture of water-soluble polypeptides originally obtained from a strain on Bacillus subtilis called Tracy back in 1943, has been used to treat topical infections but it is systemically toxic so limiting its use.
Baclofen : a derivative of GABA which was developed to elevate the inhibitory effects of GABA in the brain, ie it is a centrally acting skeletal muscle relaxant, more lipophilic than GABA, which can decrease muscle spasticity. Its site of action is primary afferent nerve terminals where is a selective agonist of GABA_B receptors causing inhibition of the release of GABA. It is used clinically to treat chronic severe spasticity (it is an antispastic).



BALB/c mouse: a common strain of laboratory mouse originating from the 'Bagg Albino' which was developed in 1913 from stock. Some commercially available BALB/c mice that are currently available have been inbred since 1923. This strain is commonly used for the in vivo production of monoclonal antibodies by the ascites method because of its histocompatibility with many hybridoma cell lines. Albino BALB/c mice are also commonly used for immunization and B cell collection. They show a low incidence of mammary tumors (about 10-20%) and a relatively high incidence of arteriosclerosis in both sexes.

Balloon injury: a method used to induce damage of the intimal tissue and endothelium and decrease the lumen diameter usually in a carotid, aortic or femoral artery of a rat, cat or pig. In this method a thin balloon is inserted into the specific artery and inflated a little so as to damage the endothelium but not to burst the vessel. Injury of the endothelial lining of the arterial wall induces an increase in vascular smooth cell proliferation. The effects of drugs on such injury and restenosis (which is a common consequence of vascular intimal injury) and the effects of anti-atherogenic drugs can then be evaluated.

Banting, Sir Frederick G (1891-1941) : Canadian physiologist who shared the Nobel prize in 1923 in Physiology or Medicine with Macleod "for the discovery of insulin".
http://nobelprize.org/medicine/laureates/1923/banting- bio.html

Barbiturates : a class of compound largely derived from barbituric acid. They have depressant effects on the central nervous system and lower muscular activity too. Depending on the dose and route of administration barbiturates are used to cause sedation, hypnosis or anaesthesia. They depress excitatory synaptic transmission particularly in the reticular activating system. They are anti-depolarizing blocking agents since they inhibit the generation of excitatory postsynaptic potentials and increase the threshold and refractory period of postsynaptic cells.



Barbiturates are both useful clinically in the treatment of severe intractable insomnia and in anaesthesia although longer-acting barbiturates are not usually the drugs of choice. The barbituric acid moiety is shown above in blue.

Barnes maze: a test to measure spatial learning and memory. Mice which have been deprived of food receive reinforcement by escaping an aversive bright light environment to a target box in a dark recessed chamber. See http://en.wikipedia.org/wiki/Barnes_maze.

Basal ganglia: structures in the cerebrum which have important functions on motor control, ie muscle movement, and which comprise the caudate nucleus, putamen, globus pallidus, claustrum and amygdaloid nucleus (although other areas of the brain may be included when referring to disorders of the basal ganglia).

Basal ganglia disorders : disorders of muscle movement caused by impaired function of one or more of the basal ganglia. These disorders can be hypokinetic, ie are infrequent and spontaneous or may be hyperkinetic and dyskinetic, ie excessive and abnormal. The main hyperkinetic disorders are the choreas (Sydenham chorea and Huntington chorea), athetosis, ballism and Wilson's disease. The most common hypokinetic disorder is Parkinson's diseases. Basal ganglia disorders are to some extent treatable with compounds which in some way compensate for the neurotransmitter excess or deficiency which causes them.

Basenji dog : a dog which doesn't bark although it isn't mute. It shows airway hyper-responsiveness with a substantial resemblance to asthma in humans and hence is used as an animal model of asthma. When these animals are challenged with bronchoconstrictors they exhibit bronchoconstriction and transient vascular leak.
Basenjis cross bred with greyhounds are known as Basenji-greyhound (BG) dogs and these have been used as an animal model of asthma because they are hyporesponsive to β-adrenergic agonist stimulation such as that caused by low concentrations of methacholine. Basenji dogs with Fanconi syndrome have been used as animal models of cystinuria.

BAT : brown adipose tissue
Bathmotropic effects: the effects of stimuli on muscle responses. Positive bathmotropic effects increase the response of muscle to stimuli, whereas negative bathmotropic effects decrease the response of muscle to stimulation.

Batrachotoxins: neurotoxic alkaloids obtained from the skin of frogs of the Phyllobates aurotaenia species which inhabit the lowland rain forests of western Columbia and which are used as poisons on blowgun darts used for hunting by some South American tribes. The batrachotoxins include homobatrachotoxin and batrachotoxin-A. They selectively stabilize the open form of neuronal sodium channels and are used as tools in the study of these channels. (The sodium channels of the species in which these alkaloids are found differ from mammalian channels and they are not sensitive to them.)

Batroxobin : a 231 amino acid serine protease and thrombin-like enzyme isolated from the venom of pit vipers (Bothrops atrox, Bothrops moojeni and Bothrops jacaraca). It forms fibrin monomer from fibrinogen which can be converted by thrombin to form a clot and so is haemostatic.

BB rat: bio-breeding rat

BBN: a carcinogen (N-butyl-N-(4-hydroxybutyl) nitrosamine) used experimentally to induce the formation of tumours in certain tissues.

BCG: the name of a vaccine originally developed in the 1930s and used for the prevention of tuberculosis. BCG stands for Mycobacterium bovis BCG (Bacillus Calmette-Guerin) and is a live but attenuated (weakened) strain of Mycobacterium bovis. Administration of BCG vaccine elicits a cell-mediated immune response that confers a variable degree of protection to infection with Mycobacterium tuberculosis. This strain of Mycobacterium bovis was named after Albert Calmette (a French bacteriologist) and Camille Guerin (a French veterinarian).

BDNF: brain-derived neurotrophic factor

Beclometasone (beclomethasone) : a potent corticosteroid that is used clinically in the prophylaxis of asthma. It reduces airway inflammation, oedema and reduces secretions of mucus into the trachea.

Bee venom test : a test for tonic pain in which a subcutaneous injection of bee venom produces local inflammation, tonic-pain responses lasting from 10 minutes to more than 1 hour and marked oedema lasting from 3 to more than 48 hours. This test has been used as a model of persistent pain.
Lariviere WR, Melzack R. The bee venom test: a new tonic-pain test. Pain (1996) 66(2-3);271-7

Behavioural despair: an animal model of depression used to screen compounds for antidepressant effects. Typically, a rat is forced to swim in a cylinder from which it cannot escape. After an initial period of vigorous activity it will adopt a characteristic immobile posture and this immobility can be decreased by antidepressants but not by minor or major tranquilizers.
Porsolt RD et al Behavioural despair in rats: a new model sensitive to antidepressant treatments. Arch Int Pharmacodyn (1977) 229; 327-336

Belladona : a mixture of alkaloids obtained from the leaves and roots of Atropa belladona. These alkaloids include hyoscyamine, hyoscine and atropine which are muscarinic receptor antagonists. This mixture has been used as an antispasmodic.

Bendrofluazide (bendroflumethiazide) : a thiazide diuretic with similar actions to hydrochlorthiazide. It has been used clinically in the treatment of familial hyperkalaemia, hypertension, oedema due to heart, liver or kidney failure and in the treatment of premenstrual oedema, and urinary tract disorders. Bendrofluazide increases potassium loss and so may be prescribed with potassium supplements.

Bennett model: a model of chronic neuropathic pain comprising loose sciatic nerve ligation which leads to peripheral mononeuropathy. It is a frequently used model of pain particularly for behavioural studies as it shows a pharmacological profile similar to that of clinical neuropathic pain. This model was developed by Gary Bennett in 1988.
Bennett GJ and Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain (1988) 33; 87-107

Benzamides : a class of antipsychotics. Examples include sulpiride, remoxipride, metoclopramide and sultopride which are all D₂ dopamine receptor antagonist. Some of these are used clinically to treat psychoses and metoclopramide is used to treat nausea and vomiting due to its central dopamine receptor antagonist actions. The benzamide moiety is shown in blue below.



Benzodiazepines : a class of benzodiazepine receptor agonist compounds which markedly affect central nervous function by causing sedation and sleep, reducing aggression and anxiety, decrease muscle tone and coordination as well as having anticonvulsant effects. They were discovered by accident in 1961 yet have become one of the most widely prescribed class of drugs. They act at GABA_A receptors to enhance the receptor response to GABA by opening GABA-activated chloride channels. They bind to a regulatory site on the receptor which is distinct from the GABA binding site to increase the affinity of GABA for the site by acting as an allosteric modulator. They bind to the α subunit which is known as the benzodiazepine receptor (BZ₁ and BZ₂ receptors) or omega receptor. The inward flow of chloride ions hyperpolarizes and stabilizes the postsynaptic membrane resulting in a decrease on neuronal firing. Benzodiazepines alone have little effect on chloride ion channel permeability but depend upon the presence of GABA for their actions. Examples of benzodiazepines include clonazepam, flunitrazepam, alprazolam, midazolam and diazepam. They are used clinically in humans to treat epilepsy, anxiety, insomnia, febrile convulsions, muscle spasm and as an adjunct to acute alcohol withdrawal syndrome. They are also to stimulate appetite (eg diazepam and oxazepam) in cats and to a lesser extent in horses dogs and goats.

Benzodiazepine receptors: a family of three receptors for benzodiazepines located on GABA_A receptors where they act as allosteric modulators. The BZ₁ (also known a omega 1) receptor subtype is located primarily in cerebellar neurons in the brain and is associated with the hypnotic and sedative activity of benzodiazepines. The BZ₂ receptor subtype (also known as omega 2) is located primarily in the primarily hippocampus in the brain and is associated with the anxiolytic, anticonvulsant, and muscle relaxant effects of benzodiazepines, and BZ₃ receptors (also known as omega 3 or BZp receptor) are located peripherally.

Benzodiazepine receptor agonists : benzodiazepines

Benzodiazepine receptor antagonists : compounds which inhibit the binding of benzodiazepines to their binding sites on GABA_A receptors preventing channel opening. Examples include flumazenil which is a pure benzodiazepine receptor antagonist and prevents benzodiazepines from binding to their receptors only and does not affect the GABA_A receptor. For this reason, it is used clinically in the treatment of a benzodiazepine overdose or for the reversal of the sedative effects of benzodiazepines in anaesthesia.

Benzodiazepine receptor inverse agonists : compounds which bind to benzodiazepine receptors but which exert the opposite effect to that of conventional benzodiazepines, ie they decrease GABA potency to produce signs of increased anxiety, muscle tension, convulsions, vigilance, and memory. Examples include FG 7142, DMCM, CGS 8216, and β-carboline ethyl ester. Inverse agonists reduce GABA-mediated Cl^- influx into neurones.

Benzoisoquinoline alkaloids: a family of alkaloids obtained mainly from plants belonging to the poppy family (Papaveraceae) and including erythrina alkaloids and curare alkaloids which in turn comprise papaverine, thebaine, codeine and morphine.

Benzothiadiazines : also referred to as thiazides, a class of diuretic and antihypertensive compounds which include indapamide, benzthiazide, fenquizone, chlorthiazide and metolazone. They all contain the benzothiadiazine ring structure which is shown in blue below.



Benzilylcholine mustard: an alkylating nitrogen mustard analogue which binds specifically and irreversibly to cholinergic muscarinic receptors. It has been used as an affinity label to isolate and study these receptors.

Benzomorphans: morphine derivatives of the methanobenzazocine family that act as potent analgesics. Examples include pentazocine, cyclazocine and N-allyl-normetazocine.

Benzothiazepines : one of five classes, three of which are used clinically, of calcium channel blockers which includes diltiazem. The other two main classes are the dihydropyridines and phenylalkylamines. The benzothiazepine moiety is shown in blue in the diagram below.



Benztropine : also known as benzatropine, an antagonist at all muscarinic receptor subtypes. Benztropine inhibits voltage-gated sodium channels and preferentially binds to the channel pore when its in the inactivated state. Benztropine also act as a histamine antagonist probably at H₁ histamine receptors and at high concentrations may act as an antagonist at nicotinic receptors. It is used clinically to treat Parkinson's disease and drug-induced extrapyramidal symptoms except tardive dyskinesia.

Benzylisoquinoliniums : a class of non-depolarizing muscle relaxants which include atacurium, cisatacurium, gallamine and mivacurium. They are competitive blockers of neuromuscular nicotinic receptors.

Bepridil : a phenylalkylamine-type calcium channel blocker used to treat angina due to its vasodilatory effects on coronary blood vessels. In in vitro studies, bepridil has also been demonstrated to inhibit the sodium inward current.

Bergström, Sune K (1916-2004) : Swedish physician who shared the Nobel prize for Physiology or Medicine with Vane and Samuelsson in 1982 for "for their discoveries concerning prostaglandins and related biologically active substances".
http://nobelprize.org/medicine/laureates/1982/bergstrom- autobio.html

Besylates (besilates) : benzenesulphonate salts. Examples include atracurium besylate (an intermediate-duration, non-depolarizing skeletal muscle relaxant) , amlodipine besylate (an antihypertensive) and mesoridazine besylate (used to treat schizophrenia). Besylates are salts of besylic acid which is also known as benzenesulphonic acid.

Beta blockers: antagonists of β-adrenoceptors. They are generally divided up into first generation (eg, propranolol, pindolol and timolol), second generation (eg, practolol, acebutolol, atenolol, metoprolol and betaxolol) and third generation (epanolol, primidolol and xamoterol) and are used cinically to treat hypertension and asthma depending on their activity at β₁ or β₂ receptors. See table under adrenoceptors.

Bethanecol: a parasympathomimetic agent with muscarinic receptor agonist effects which is used clinically to treat urinary disorders particularly urinary retention as it primarily affects the urinary bladder and gut. It has also been used to increase gastrointestinal motility and functions as a stimulant laxative. It contracts the detrusor muscle in the bladder leading to bladder emptying. Bethanechol is not metabolised by acetylcholinesterases but its effects can be antagonised by atropine.
Bestatin: an immunomodulator, an antibiotic and a potent inhibitor of some aminopeptidases. It is used as a tool to investigate the physiological role of exopeptidases in the control of the immune system, in the growth of tumors, in tumour metastases and in the degradation of cellular proteins. It has been used as an anticancer drug to prolong remission.
Scornik OA, Botbol V. Bestatin as an experimental tool in mammals. Curr Drug Metab (2001) 2(1); 67-85

Betaxolol : a selective β₁-adrenoceptor antagonist used in the treatment of hypertension and glaucoma. Betaxolol is cardioselective but not cardiospecific as it still has some β₂-receptor (present in the bronchus) antagonist effects.

Betel : a nut used in ethnopharmacology.

BEW : base equivalent weight

Bezafibrate : a fibrate used clinically to treat type IIa, IIb, III, IV and V hyperlipidaemias.

Bezold-Jarish (BJ) reflex : also referred to as the von Bezold-Jarish reflex, a cardiovascular reflex occurring due to stimulation of chemoreceptors primarily distributed in the left ventricle. Stimulation can be caused by certain antihypertensive alkaloids and other substances. From the heart, vagal fibers carry the impulses to the medulla oblongata. From here efferent vagal fibers cause reflex bradycardia and hypotension which can easily be monitored. This reflex is used to test the effects of 5-HT₃ receptor antagonists.

BHA : butylated hydroxyanisole

BHI : brain-heart infusion

BHK : baby hamster kidney.

b.i.d. : bis in die, twice a day and a term use in prescribing.

Bicuculline : an alkaloid obtained from Dicentra cucullaria, Aldumia fungosa and several species of Corydalis sp, it a classical GABA_A antagonist, a neurotoxin and neuroconvulsant and a tool for the study of GABA receptors and convulsions.

Bicuculline seizure threshold test : a test for the effects of anticonvulsant drugs. Typically, bicuculline at a dose of about 2.5mg/kg is administered often by infusion to mice to the point at which seizures are induced the endpoint being taken as the first myoclonic jerk of the head and neck. This is repeated after administration of the test anticonvulsant and an increase in this threshold is seen as a measure of the efficacy of anticonvulsants.

Bicyclams : a class of low molecular weight antiviral compounds which are highly potent and selective inhibitors of the replication of HIV-1 and HIV-2 strains. They specifically block CXCR4 (fusin), the receptor for the CXC chemokine SDF-1 (soluble-derived factor), which also functions as a co-receptor by T-lymphotropic HIV strains facilitating entry into their target cells. They block the early step in the life cycle of a virus by interfering with viral uncoating.
De Vreese K, et al. The bicyclams, a new class of potent human immunodeficiency virus inhibitors, block viral entry after binding. Antiviral Res (1996) 29; 209-19

Biguanides : a class or orally active hypoglycaemic agents that do not require functioning pancreatic β-cells. They increase the uptake of glucose by skeletal muscles. Examples include metformin which is used clinically to treat type 2 diabetics or obese patients who fail to respond to diet treatment and phenformin. The guanidine moiety is shown in red.



Bile acid sequestrants : also known as bile acid binding resins, compounds which sequester (bind to) bile acids in the gut to prevent their reabsorption and enterohepatic recirculation. They are used clinically to decrease cholesterol absorption in the gut so lower blood LDL-cholesterol in the treatment of hypercholesterolemia and related cardiovascular diseases. Examples include cholestyramine and colestipol both of which are anion exchange resins

Binding assays : also known as affinity assays, a method of determining the affinity of a ligand for a receptor whether its is an agonist or an antagonist at that receptor site.

Binding site : any site on a receptor or enzyme to which a ligand attaches.

Binomial distribution: a form of distribution and probably the most commonly used discrete probability distribution in statistics. It describes a situation in which the experiment consists of n identical trials where n is determined in advance, each trial has two possible outcomes such as pass or fail, increase or decrease, the trials are independent so that the outcome of one trial has no effect on the outcome of another, and the probability of success is constant from one trial to another. The binomial distribution describes the outcome of flipping a coin repeatedly where the result can be heads or tails or in drug toxicity testing where the outcome is died or survived.

Bioassay : an assay to determine the concentration or potency of a substance by measuring the biological response that substance elicits in cells, tissues or organs.

Bioavailability : a means of expressing the amount of a dose of drug entering the systemic circulation and being available to the tissues, ie the target tissue and all other tissues where it is distributed. Bioavailability is described in terms of relative bioavailability and absolute bioavailability.

Bio-breeding (BB) rat: rats susceptible to the induction and development of insulin-dependent diabetes mellitus (IDDM). Diabetes in these rats is due to autoimmune destruction of pancreatic β-cells and so shares many features with human type 1 diabetes. Thus BB rats are spontaneously diabetic and are used in studies of diabetes and in the evaluation of hypoglycaemics.
Ramanathan S, Poussier P. BB rat lyp mutation and Type 1 diabetes. Immunol Rev (2001) 184;161-171

Bioequivalence : a term used in pharmacokinetics to express the expected in vivo biological equivalence of two proprietary preparations of a drug. If two drug preparations are bioequivalent they have the same bioavailability, duration of action and efficacy.

Biogenic amine : naturally occurring amines which are physiologically and/or pharmacologically active. They include neurotransmitters, eg adrenaline, noradrenaline, dopamine, serotonin, acetylcholine, histamine and serotonin.

Biogenic substances: aliphatic, alicyclic and heterocyclic compounds usually of low molecular weight which are produced by cellular metabolism. Biogenic amines include metabolites of amino acids such as histamine and serotonin.

Bioisostere : chemical substituents or groups in a molecule which do not necessarily have the same size or volume (unlike isosteres) but which have similar chemical or biological properties thus giving the molecule similar biological properties to a chemically related compound.

Bioisosteric replacement : the replacement within a bioactive molecule of a functional group by another group or moiety that may have similar charge, size or hydrogen-bonding capabilities usually with the intention of increasing the bioactivity, selectivity and ADME characteristics. Bioisosteric replacement is common in the search for new drugs.

Biological response modifier (BRM) : a term introduced in the late 1970s by the National Cancer Institute in the US to describe a group of molecules which modify immune responses and responses to tumor cells. This family of compounds includes cytokines, interleukins and immune effectors.

Biopharmaceutics : the study of the effects of pharmaceutical formulations on the pharmacodynamics and pharmacokinetics of active drug in the formulation. Important factors in biopharmaceutics include the shape, taste and colour of the formulation, the chemical characteristics of the excipients such as fillers, binders, disintegrants and lubricants, particle size, the solubility, stability of active components such as their acid lability, nature of the coatings of orally administered formulations and the presence of impurities. All of these factors may influence the therapeutic usefulness of the drug.

Biophase : a zone or area in which drug molecules come into contact with their site of action and a term first described by Furchgott in 1955. Examples of a biophase include the synaptic cleft at a neuromuscular junction for the neuromuscular blocker suxamethonium or the plasma for warfarin.
Furchgott RF. The pharmacology of vascular smooth muscle. Pharmacol Rev (1955) 7; 183-265

Bioprecursors : prodrugs which are chemically modified in the body the modification of which generates a new compound which is either active or which can be transformed metabolically or chemically to form an active compound.

Bioreductive drugs: compounds which are chemically reduced in areas of tissue in which oxygen tension is low such as in the hypoxic cells of tumors. Examples include tirapazamine (a hypoxic tissue-selective cytotoxin) which has been shown to exhibit greatly enhanced cytotoxicity in hypoxic tumor cells particularly when combined with other antitumour drugs. Tirapazamine is metabolism by reductases in tumor cells to form an oxidising radical which can be efficiently scavenged by molecular oxygen in normal tissues to reform the parent compound. In hypoxic tissues however, the oxidising radical removes a proton from DNA to form DNA radicals causing cytotoxic DNA strand breaks.

Biotransformation: the chemical and enzymic modification which is undergone by a drug as it passes through the body, ie anytime between administration and excretion. Biotransformation processes also occur in in vitro in metabolic models. Often the result of biotransformation is a more potent compound as in the case of a prodrug activation or a less potent or inactive compound in the case of detoxification. The term biotransformation is preferred by some to drug metabolism and includes conjugation reactions. Biotransformation also indicates the enzymic conversion and modification of substrates to form target molecules in chemical synthesis. It is applied where conventional chemical synthesis would be slow, expensive, technically difficult or require hazardous reagents. Examples include the production of vitamin C, semisynthetic penicillins and atenolol.
Glazer and Nikaido. Microbial Biotechnology, Ch 14 (Organic Synthesis). W.H. Freeman and Co, (1995)

Biotranslocation : the movement of drugs into, through and out of the body and its compartments. This involves mechanisms underlying molecular transport such as diffusion or active transport and an understanding of factors which affect this mobility such as pH, ionic concentration, molecular weight and lipophilicity and hydrophilicity.

Biphasic : characterized by having two phases. Metabolism of some drugs, for example, can be biphasic. The first phase involves oxidations, reductions, and hydrolyses and the second comprises conjugation reactions the rates of these reactions often being different.

Biphasic insulin : a preparation of insulin which is a mixture of intermediate- and fast-acting insulin.

Biphenyltetrazoles: a class of antihypertensives and which include the sartans, eg losartan, valsartan and candesartan. They all contain the biphenyltetrazole group shown in blue in the diagram.



Bipolar disorder : also known as manic-depressive illness, a brain disorder that causes unusual shifts in a person's mood from energetic (highs) to depression and feelings of sadness (lows) with loss of the ability to carry out daily functions. Bipolar disorders are often treated with mood stabilizers such as lithium, valproate or carbamazepine. Antipsychotics such as clozapine, calcium channel blockers such as verapamil and newer anticonvulsants such as lamotrigine may also be beneficial.

Bisoprolol: a selective β₁- adrenoceptor antagonist used clinically to treat hypertension and angina. Like many β-blockers such as atenolol, betaxolol, metoprolol and nebivolol, it is relatively cardioselective but not cardiospecific and does have weak effects on bronchial β₂-adrenoceptors.

Bisphosphonates: compounds used to treat bone disorders such as osteoporosis. They inhibit osteoclast-mediated bone resorption and to decrease the release of calcium and other minerals into the blood. They are absorbed into hydroxyapatite crystals in bone slowing both the rate of growth of bone and its dissolution so reducing the rate of bone turnover. They also have potent antitumour activity. Examples include pamidronate, alendronate (alendronic acid), risedronate, etidronate and zoledronate (zoledronic acid). The bisphosphonate moiety is shown in blue in the diagram below.



Bisprasin: a cytotoxic bromotyrosine derivative and Ca²⁺ releaser with caffeine-like properties obtained from a marine sponge of the genus Dysidea .

Biventer cervicus: a muscular extension of the spinalis cervicis to the occipital bone sometimes fusing with semispinalis capitis and a muscle which functions to extend the neck. Biventer cervicus neuromuscular preparations typically from 3-13-day-old chicks are used in the investigation of cholinergic transmission. The chick biventer cervicis muscle contains both focally innervated twitch fibres and multiply innervated contracture-producing fibres and can be stimulated by exogenous application of cholinomimetic agonists as well as stimulation of its motor nerve allowing prejunctional effects to be distinguished from postjunctional effects.
Ginsborg BL, Warriner J. The isolated chick biventer cervicis nerve muscle preparation. Br J Pharmacol Chemother. 1960;15:410-5

Black, James W (1924 - 2010): British physician and pharmacologist who shared the Nobel Prize for Physiology or Medicine in 1988 with Elion and Hitchings 'for their discoveries of important principles for drug treatment'. He accepted Ahlquist's idea that two distinct adrenoceptors existed and realized the great pharmacotherapeutic potential of selective receptor blocking drugs in reducing myocardial oxygen demand. In 1964 he lead a team that developed the first clinically useful β-adrenoceptor blocking drug, propranolol. This type of drug is used in the treatment of coronary heart disease (angina pectoris, myocardial infarction) and hypertension. In 1972 Black characterized a new group of histamine receptors, H₂-receptors, and subsequently developed the first clinically useful H₂-receptor antagonist, cimetidine. He now heads the James Black Foundation in London, UK.
http://nobelprize.org/medicine/laureates/1988/black- autobio.html

Black and Leff model: a 'operational model' of agonism to help explain the action of agonists and partial agonists. Black and Leff also developed experimental methods to determine the affinity of agonist binding and a way to measure relative agonist efficacy based on the dose-response curves.
Black JW and Leff P. Operational models of pharmacological agonism. Proc R Soc Lond (1983) 220; 141-162

Black widow spider venom: also known as latrotoxin (LTX), the toxic protein fraction from the venom of spiders of the genus Latrodectus such as Latrodectus mactans. This venom has a molecular weight of 5000 and is neurotoxic. It causes a massive release in vesicle-bound ACh and noradrenaline release and destruction of prejunctional nerve terminals.

Blasticidins: pyrimidine antibiotics which inhibit the growth of some fungi and bacteria. They are produced by Streptomyces griseochromogenes and inhibit peptide chain elongation during protein synthesis in fungi.
Blasticidin A - a potent inhibitor of aflatoxin production.
Blasticidin S - a potent antifungal and cytotoxic peptidyl nucleoside antibiotic. It is a peptidylpeptidase inhibitor and a non-competitive inhibitor of ribonuclease P.

Bleomycins: a class of glycopeptide antibiotics produced by Streptomyces verticillus and used as a mixture for the treatment of squamous cell carcinomas, testicular cancer and lymphomas About 200 different bleomycins are known although few are used clinically. They cause strand breakage and fragmentation in DNA. Examples include bleomycins A₂, A₂I and B₁.

Blind experiment: a type of experiment in which the identity of the product or compound being tested in not known to either some or all of the participants, ie observer and subjects. The purpose of this type of experiment is to prevent a biased interpretation of the observed effects by either the subject or the observer (experimenter or physician) although, in the case of a clinical trial, both parties will have an understanding of the purpose of the investigation, the nature of the drug being investigated and potential side effects. Blind experiments are not limited to those involving only human subjects but are often used in the laboratory. A single-blind experiment is one in which one participant most often the subject is not informed of the identity of the test product but the observer is. In a double-blind experiment neither the subject nor the observer know the identity of the test product. In a triple-blind experiment neither the subject, the observer nor the person responsible for drug administration such as a nurse know the identity of the test product.

BLNAR: β -lactamase non- producing ampicillin resistant influenza, strains of influenza which are resistant to ampicillin and which are common in Japan probably due to excessive use of ampicillin.

β-blockers: β-adrenoceptor antagonists

Blockbuster: a term applied to a drug which, following release onto the market, surpasses all sales predictions and easily recoups its development costs eventually providing a healthy profit for manufacturer. Examples of such drugs include cimetidine (an H₂ blocker for the treatment of gastric and duodenal ulcers) and Viagra (a phosphodiesterase V inhibitor for the treatment of erectile dysfunction).

Bowman-Birk inhibitor: a serine protease inhibitor derived from soy beans which has anticancer effects and is being evaluated for its effects on smooth muscle. It has been shown to have chemoprevention activity in in vitro and animal systems including the hamster cheek pouch model.

B_max: the maximum amount of a drug that can bind to receptors usually expressed in picomoles of drug per mg protein.

BMD: bone mineral density

BMP: bone morphogenic protein

BMY 7378: a selective antagonist of 1D-adrenoceptors and a 5-HT_1A partial agonist used in the investigation of these receptors.
Sharp T et al. Further investigation of the in vivo pharmacological properties of the putative 5-HT1A antagonist, BMY 7378. Eur J Pharmacol (1990) 176; 331

BN rat: brown-Norway rat

BNK rat: brown Norway katholiek rat

Body packing: a form of drug smuggling in which a drug of abuse, usually with a high street value, is packed into small packages such as tied-off condoms, swallowed and carried into another country while in the large intestine of the smuggler. These packages can later be recovered by bowel opening. Rupture of these packages while in the intestine usually causes death.

Bolus: a single dose of drug usually injected into a blood vessel over a short period of time or a mass of chewed food usually passing along the gastrointestinal tract.

Bombesin: a tetradecapeptide (14 amino acids) originally isolated from the skin of certain European fire belly frogs such as Bombina bombina and Bombina variegata which stimulates gastric acid secretion by causing the release of gastrin. It also stimulates the release of pancreatic and adenohypophyseal hormones and causes contraction of gastric, urinary tract and uterine smooth muscle. The mammalian equivalents of frog bombesin are neuromedin B and gastrin-releasing peptide as well as the biologically active gastrin-releasing peptide fragment neuromedin C. Bombesin is thought to play a role in obesity and has been implicated as a growth factor in a variety of gastrointestinal tumors. The amino acid sequence of bombesin is shown below.



Bombesinergic : relating to the synthesis, storage and release of bombesin.

Bombesin receptors: receptors for bombesin of which (probably) four are known; BB1 (also known as neuromedin B-preferring receptor), BB2(also known as a gastrin-releasing peptide-preferring receptor) ,BB3 (an orphan receptor also known as BRS3) and BB4). They are all coupled to the phospholipase C signaling pathway. Bombesin receptors are widely distributed in the CNS, lungs and oesophagus and play a variety of physiological roles including modulating satiety, thermoregulation and circadian rhythms. They also modulate the activity of serotoninergic mechanisms in the CNS and so play a role in sleep and depression. Bombesin receptors mediate smooth muscle contraction in the gut, pancreatic secretions and the release of gastrin.
Merali Z, McIntosh J, Anisman H. Role of bombesin-related peptides in the control of food intake. Neuropeptides (1999) Oct 33(5); 376-86
http://www.iuphar-db.org/GPCR/ChapterMenuForward? chapterID=1325

Bombesin receptor agonists: compounds which agonize bombesin receptors. Examples include PD165929 and PD168368 (BB1-selective).

Bombesin receptor antagonists: compounds which antagonize bombesin receptors. Examples include [D-Phe12]-bombesin and [Tyr4, D-Phe12]-bombesin.

Bone resorption inhibitors: anti-osteoporotics

Bonnet monkeys: a species of monkey (Macaca radiata) often used in reproductive studies.

BOP: N-Nitrosobis(2-oxopropyl) amine

Bovet, Daniel (1907-1992): Swiss-born physiologist who won the 1957 Nobel Prize for Physiology or Medicine "for his discoveries relating to synthetic compounds that inhibit the action of certain body substances, and especially their action on the vascular system and the skeletal muscles". Bovet discovered in 1937 that the adrenaline antagonist thymoxyethyldiethylamine also blocked the actions of histamine.
http://nobelprize.org/medicine/laureates/1957/bovet- bio.html

Bovine: relating to cattle.

BP: B ritish Pharmacopoeia, a compendium of drugs data for drugs prescribed in the UK.

BQ-123: a selective ET_A endothelin receptor antagonist.

BQ-3020: a highly potent and selective ET_B endothelin receptor agonist.

Bradykinin: also known as kallidin I and kinin 9, a nonapeptide (9 amino acids) and one of a groups of plasma peptides referred to as kinins. It is produced from a plasma precursor by the enzyme kallikrein, trypsin or plasmin and causes dilation of blood vessels, a decrease in blood pressure, contracts bronchial, intestinal and uterine smooth muscle to contract and is a potent pain producer.

Bradykinin receptor: a family of two or three receptors, B₁, B₂ and B₃. B₁ bradykinin receptor whose ligand is Lys-des-Arg-bradykinin and B₂ bradykinin receptor whose ligand is bradykinin. Both receptors are members of the family of 7-transmembrane G protein-coupled receptors. Human B₂ receptors (364 amino acids) are present in most tissues and mediate most of the classic inflammatory effects of kinins including vasodilation, vascular permeability, pain, synthesis of eicosanoids and smooth muscle contraction. Human B1 receptors (353 amino acids) are not usually present but are upregulated over a matter of hours by noxious stimuli such as lipopolysaccharide, interleukin-1 and epidermal growth factor.
http://www.iuphar-db.org/GPCR/ChapterMenuForward? chapterID=1330

Bradykinin receptor agonists: compounds which agonise bradykinin receptors. Examples include labradimil (once known as RMP-7) and a 9 amino acid B₂-selective agonist being developed as a drug which facilitates the entry of other drugs across the blood-brain barrier.

Bradykinin receptor antagonists: compounds being developed for the treatment of pain and inflammation. Examples include bradyzide (a potent, non-peptide B₂ receptor antagonist) and FR 173657 (both are non-peptides and are referred to as 3^rd generation bradykinin antagonists).

Bradyzide; a potent, non-peptide B₂ bradykinin receptor antagonist with long -lasting oral activity in animal models of inflammation and hyperalgesia.

Brain natriuretic peptides: a form of natriuretic peptide.

Brevetoxins (PbTx): a class of about 10 lipid-soluble polyether neurotoxins produced by the marine dinoflagellate Karina brevis and which are responsible for neurotoxic shellfish poisoning. PbTx binds to site 5 of the voltage-gated sodium channel of excitable membranes and are used as a pharmacological tool to investigate sodium channels.

Briard dog: an animal model of congenital stationary night blindness and canine retinal dystrophy.
Narfstrom K et al. The Briard dog: a new animal model of congenital stationary night blindness. Br J Ophthalmol (1989) 73(9); 750-756

Bridging study: a type of clinical investigation which bridges studies carried out in different countries. For example, from a study carried out in a Western country to a Japanese trial where clinical trial subjects are genetically different. The idea is to run the full development in the West (Europe and the US for example) and then bridge to a smaller development in Japan. Bridging studies are usually comprised of a healthy volunteer study usually with single doses so a single dose comparison can be made between the two populations (eg Asians and Caucasians), a Phase II dose-ranging study to demonstrate dose comparability and a single pivotal trial in patients to demonstrate that disease processes are similar. The number of bridging studies carried out depends on the similarity of the disease in the populations or countries of interest.

Brindled mottled mouse (Mobr): an animal model of the Menkes' copper deficiency syndrome.

BRL37344: a selective β₃- adrenoceptor agonist which has been shown to cause dose-dependent decreases in energy expenditure and weight loss in rats.

BRL44408: a selective antagonist of α_2A-adrenoceptors.

BRL48962: a selective antagonist of α_2A-adrenoceptors.

BRM: biological response modifier

Broad-spectrum : usually an antibiotic or antifungal which has a wide range of antimicrobial actions especially against gram-positive and gram-negative bacteria.

Bromism: chronic poisoning with bromine and once a side effect of treatment of epilepsy with bromide salts in the mid 1800s.

3-Bromoacetonyltrimethylammonium bromide: also known as bromoketone, an irreversible inhibitor of choline acetyltransferase.

Bromocriptine: an ergot alkaloid and potent selective D₂ dopamine receptor agonist. It inhibits prolactin release from the pituitary and is used clinically to treat hormone and hormone-related disorders such as galactorrhoea, hypogonadism, benign breast cancer and acromegaly. It has also been used to treat Parkinson's disease because it directly stimulates central dopamine receptor.

Bronchodilators : compounds causing the relaxation of bronchial smooth muscle thereby decreasing airways resistance and facilitating easier breathing. Useful in asthmatics where bronchoconstriction is a problem. Examples include the b₂-adrenoceptor agonist salbutamol.

Brown-Norway rat (BN rat): a strain of inbred laboratory rat which is susceptible to the development of lesions in the internal elastic lamina of the abdominal aorta. They are used in studies of cardiovascular disease.

Brown Norway Katholiek (BNK) rats: rats which are deficient in the kinin precursor kininogen due to a mutation in the kininogen gene. They have been used to study the kallikrein-kinin system and the physiological effects of kinins.

Brucine: a toxic alkaloid and neurostimulant (10, 11-dimethoxystrychnine). It has about 1/10^th the toxicity of strychnine and similarly exhibits paralysis of smooth muscles.

Bryostatins: a group of over 13 macrocyclic lactones obtained from the marine sponge (marine bryozoan) (Bugula neritina). Bryostatins are powerful activators of protein kinase C and they have significant antitumor activity against lymphomas, leukaemia cells, melanoma cells and breast cancer cell lines.

BSO: buthionine sulphoximine

Buccal administration: dosing of a solid preparation of a drug where it is placed between the jaw and cheek and slowly allowed to dissolve. It is similar in pharmacokinetics to sublingual administration.

Bufadienolides: a family of about 12 cardiotonic steroids  including bufalin and bufotalin and similar to cardenolides originally isolated from toads of the family Bufonidae but which can also be found in many other animals and plants such as in the leaves of Kalanchoe pinnata and Kalanchoe daigremontiana. Bufadienolides have potent immunosuppressant effects and digoxin-like effects of heart muscle. They also have insecticidal effects.

Buffalo rat: a strain of rat first developed in 1946 which shows spontaneous tumours of the anterior pituitary in about 30% of animals and in the adrenal cortex in about 25% of older animals. There is a low incidence of renal neoplasms and a low incidence of dental caries.

Bufogenins: compounds which are similar to cardiac glycosides and present in the poison glands of toads. They inhibit Na⁺/K⁺-ATPase activity in the myocardial cell membrane which leads to an increase in the intracellular sodium-calcium exchange and an increase in calcium concentrations in the myocardial cells resulting in the arrhythmias. Bufogenins also block sodium channels in a similar manner to local anesthetics. Examples include marinobufagin.

Bufotoxin: a bufogenin (bufadienolide) toxin and the principal toxin in the skin venom of the European toad, Bufo vulgaris. Bufotoxin has a digitalis-like effect on the heart.

Bumetanide: a sulphonamide derivative and a potent loop (high ceiling) diuretic developed in the early 1960s and still used clinically to treat oedema and oligouria due to renal failure. It inhibits resorption of Na⁺ and water from the ascending loop of Henle.

Bungarotoxins (BTX): a group of animal neurotoxins obtained from the venom of elapid snakes Bungarus multicinctus (Taiwanese banded krait) and Bungarus caerulus (Indian krait). Two common members of this group are α-bungarotoxin and β-bungarotoxin and both are used as tools to study cholinergic function.
α -Bungarotoxin is the main component in elapid venom, it comprises a single polypeptide chain of 74 amino acids and is a highly specific blocker of post-synaptic nicotinic acetylcholine receptors in skeletal muscle.
β- Bungarotoxin is a dimer and comprises an A chain (71 amino acids) and a B chain (60 amino acids) which acts presynaptically to block transmitter release.

Buspirone: a drug used clinically for the short term treatment of anxiety. It is a classical 5-HT_1A receptor partial agonist.

Buserelin: a gonadorelin analogue used clinically to treat endometriosis, infertility, anaemia due to uterine fibroids and prostate cancer. It has gonadotrophin-releasing hormone agonist actions and stimulates gonadotrophin release which in turn desensitizes the pituitary gland and inhibits the production of gonadotrophin. Such gonadal suppression is desirable to treat endometriosis and sex hormone-dependent tumours.

Buthionine sulphoximine (BSO): a glutathione-depleting agent used experimentally to induce cataracts as this eye disorders is associated with glutathione deficiency. D,L-buthionine-(SR)-sulphoximine is a selective inhibitor of gamma-glutamylcysteine synthetase which is the rate-limiting step in glutathione biosynthesis. BSO reduces glutathione levels in tissues by preventing cysteine utilization for glutathione resynthesis. Glutathione is known to protect cells against the toxicity of certain drugs and reactive intermediates.

Butoxamine: a β₂ adrenoceptor antagonist and weak α-agonist used as a pharmacological tool. It inhibits fatty acid metabolism and has hypoglycemic and antihyperlipidemic actions.

Butyrycholinesterase: also known as pseudocholinesterase, a cholinesterase.

Butylated hydroxyanisole (BHA) : a carcinogen used in the induction of forestomach cancers in experimental animals especially hamsters and mice.

Butyrophenones: also known as piperidine butyrophenones, a class of antipsychotic drug used to treat schizophrenia, psychoses and movement disorders such as motor tics and choreas. Examples include haloperidol, bromperidol, moperone, fluanisone, trifulperidol, pipamperone, spiperone, timiperone, droperidol and benperidol. Butyrophenones are D₂ dopamine receptor antagonists and they all have a common structural feature shown in blue in the figure of haloperidol below.

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