m2-toxin: a selective ligand for M₂ muscarinic receptors obtained from the venom of the east African green mamba (Dendroaspis angusticeps).
Jigany MC et al. m2-Toxin: A Selective Ligand for M2 Muscarinic Receptors. Molecular Pharmacology (1999) 56 (5): 933-937

M-6434: a non-subtype selective agonist of α₁-adrenoceptors with vasoconstricting actions. It has been used as a pharmacological tool to investigate adrenoceptors.
Ohnishi H et al. Pharmacological properties of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434). Arzneimittelforschung (1981) 31(9):1425-9

MAb: monoclonal antibody

MAC: minimum alveolar concentration

Macleod, John JR (1876 - 1935): Scottish-born Canadian physiologist who shared the 1923 Nobel Prize for Physiology and Medicine with Banting 'for the discovery of insulin'.
http://nobelprize.org/medicine/laureates/1923/macleod- bio.html

Macrolides: a class of antibiotics effective in the treatment of gram-positive bacteria. They inhibit bacterial protein synthesis by binding to the 50S subunit of bacterial ribosomes (the same binding site as that for chloramphenicol and clindamycin) and inhibit the translocation of aminoacyl t-RNA. They are usually bacteriostatic but at high concentrations are bactericidal. Examples include erythromycin, azithromycin, clarithromycin, oleandromycin and troleandromycin. The name macrolide derives from their large size (typically 14 or 16 carbon atoms) and that they are lactones (which are cyclic esters).

Macrophage inflammatory protein: a murine CXC chemokine induced by LPS, TNF-α and IL-1 . It upregulates the production of neutrophil integrin (CD11b/CD18), stimulated neutrophil respiratory burst and acts as a neutrophil chemmoattractant.

Macular mutant mice: an animal model of Menkes' kinky-hair disease.
Shiraishi N et al. Copper metabolism in the macular mutant mouse: an animal model of Menkes's kinky-hair disease. Biol Neonate (1988) 54(3):173-80

Maculotoxin: a neurotoxin obtained from the venom glands of the blue-ringed octopus Hapalochlaena maculosa and now known to be the same as tetrodotoxin. It acts by blocking sodium channels in neurones.

Magnus bath: a small glass container in which tissue can be suspended in solution to observe the effects of drugs on it. Named after the German physiologist Rudolf Magnus (1873-1927).

MAIDS: murine acquired immunodeficiency syndrome, the mouse and rat equivalent of AIDS.

Maitotoxin (MTX): a potent marine dinoflagellate toxin and a potent activator of voltage-sensitive calcium channels and increases the flow of Ca2+ ions across a variety of cell membranes. It has been used as a pharmacological tool.

Major tranquilizers: also known as antipsychotics.

Mamba toxins: protein toxins from black (Dendroaspis polylepis) and green (Dendroaspis angusticeps) mamba snakes. They are neurotoxins and include dendrotoxins which have little or no antiprotease activity but block certain neuronal voltage-dependent potassium channel subtypes of the Kv1 subfamily. They are often used as pharmacological tools in the study of K⁺ channels.
Harvey AL. Twenty years of dendrotoxins. Toxicon (2001) 39(1):15-26

Mammalian cell transformation test: tests using cultured mammalian cell systems to detect phenotypic changes in vitro which are induced by chemical substances associated with malignant transformation in vivo.

Mammillary model: a pharmacokinetic model which represents the human body by a limited set of compartments which usually have no physiological or anatomical equivalent. This model has a central compartment surrounded by others connected only to the central compartment, ie the compartments are in parallel. The name is derived from the Latin word for breast. See also catenary model.

Mancude ring: a ring in an organic molecule having the maximum number of noncumulative double bonds. Common examples in medicinal chemistry include benzene, indene and indole.

Mann-Whitney U-test: also referred to as the Wilcoxon Rank-sum test, a statistical method for the comparison of two completely independent random samples (x and y). It was proposed by Mann and Whitney (in 1947) and by Wilcoxon (in 1947) as a test to determine whether the degree of overlap between the the observed distributions of the groups is less than that expected by chance. The null hypothesis that the two samples are drawn from a single population (and there are no differences between the populations).

Mannoproteins: branched a-linked mannose polymers linked to proteins via an N-acetylglucosamine-N-acetylglucosamine moiety. They are essential components of fungal cell membranes.

Mannoprotein binders: also known as mannoprotein inhibitors, a class of antifungal compounds which bind to fungal wall mannoproteins causing the cell to leak its intracellular components leading to cell death. Examples include the pradimicins and benanomicins.

Manumycins: a class of antibiotic isolated from Streptomyces spp such as Streptomyces nodosus. Manumycin A is a farnesyltransferase inhibitor which can induce apoptosis in tumor cells.

MAO: monoamine oxidase

MAOI: monoamine oxidase inhibitor

MAP kinases (mitogen-activated protein kinase): a family of about 13 cellular enzymes which are stimulated by extracellular stimuli such as mitogens and which have a broad range of cellular functions such as gene expression, cell differentiation, apoptosis and mitosis. Several groups of MAP kinases exist including the ERK1/ERK2 MAP kinase cascade which is activated by a variety of hormones and growth factors.
Another group of MAP kinases are potently activated by cellular stress and this group includes the c-Jun amino terminal kinases (JNKs) and p38 MAP kinase isoforms. These enzymes are important targets for anticancer therapy.

Marble burying: an animal model for both anxiety and obsessive compulsive disorders. Typically, mice are individually housed in cages containing 5cm of hard wood bedding and marbles are placed in each cage. Mice pretreated with anxiolytic agents show less marble burying behaviour compared to untreated mice.

Margatoxin (MgTX): a 39 amino acid peptide and voltage-dependent potassium channel blocker isolated from the venom of the scorpion (Centruroides margaritatus). It has been used as a pharmacological tool to investigate potassium channels.
Garcia-Calvo M et al. Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels. J Biol Chem(1993) 268; 18866-74
See also http://www.jbc.org/cgi/reprint/268/25/18866.pdf

Mast cells: cells found in connective tissue and which produce an exclusive family of proteases (tryptases and chymases) along with mediators of inflammation such as histamine and eicosanoids. They play an important role in allergy and anaphylaxis. See http://en.wikipedia.org/wiki/Mast_cell

Mast cell stabilizers: also known as mast cell degranulation inhibitors, compounds which prevent mast cells from releasing pro-inflammatory compounds such s histamine and eicosanoids which are present in their storage vesicles. Mast cell stabilizers include cromoglicate sodium and are used in the treatment of allergies, food allergies, asthma, allergic conjunctivitis and allergic rhinitis.

Mastoparan: a mast cell degranulating peptide and toxin obtained from the venom of Vespula lewisii, the yellow jacket wasp. It is a tetradecapeptide which acts as a calmodulin antagonist and activates phospholipase A₂.
Higashijima T et al . Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins) J Biol Chem (1988) 263; 6491 See http://www.jbc.org/cgi/reprint/263/14/6491.pdf

Matlystatins: a group of type IV collagenase inhibitors isolated from the bacterium Actinomadura atramentaria. Matlystatins A, B, D, E and F are known.

Matrixins: also known as matrix metalloproteases.

Maurotoxin (MTX): a basic, single chain 34 amino acid polypeptide and potassium channel blocker obtained from the Tunisian chactoid scorpion Scorpio maurus. It shows 29-68% sequence identity with other potassium channel toxins and has been used as a pharmacological tool to study potassium channels.

Maximal agonist effect (MAE): also known as intrinsic effect (although maximal agonist effect is the preferred term), a measure of the ability of a compound to elicit receptor activation and a physiological or pharmacological response such as changes in enzyme activity or contraction of an isolated muscular tissue. The maximal response attainable by an agonist is 100% and this is equivalent to an intrinsic activity value of 1.0. Partial agonists have values of less than one and antagonists, which bind to the receptor but which do not elicit any response have a value of zero. Inverse agonists, however, have intrinsic activity values from zero to minus 1.0. Super agonists, on the other hand, have values above 1.0.

Maximal electroshock seizure (MES) test: a method to test the effects of anticonvulsant drugs. Typically, the test drug is given about 45 minutes prior to the application of an alternating current of 50 Hz and 150 mA applied via bicorneal electrodes for 0.2 sec. MES causes tonic convulsions of the hindlimb (tonic extension) and the duration of the convulsion, effects on seizure protection and mortality are taken as indicators of the efficacy of the test drug.

MCA: middle cerebral artery, a common site for occlusion to induce focal ischaemia in the brain.

MCAO: middle cerebral artery occlusion.

MCH: melanin-concentrating hormone

MCI- 186: a radical scavenger (3-methyl-1-phenyl-2-pyrazolin-5-one ) and anti-oxidant compound. It has been shown to protect animals against the effects of ischaemia probably by inhibiting lipoxygenases.

McN-A- 343: an M₁ muscarinic receptor agonist and postganglionic nicotinic receptor agonist (4-(m-chlorophenyl-carbamoyloxy)-2- butynyltrimethylammonium chloride) used as a pharmacological tool to investigate these receptors and postganglionic nicotinic receptors.

MDA: methylenedioxyamphetamine (also known as tenamfetamine), a hallucinogen, designer drug and drug of abuse. It is also known as the 'love drug' and 'mellow drug of America'.

MDMA: 3,4-methylenedioxymethamphetamine, a recreational drug more commonly known as ecstasy.

MDR: multidrug resistance

MDR: mitochondrial diazepam binding inhibitor receptor

MDX mouse: an animal model for Duchenne and Becker muscular dystrophy  (DMD/BMD) which lacks the muscle protein dystrophin. This mutation is X chromosome-linked and this defect produces viable animals which have high serum levels of muscle enzymes and have histological lesions similar to those found in human muscular dystrophy.

Me-again drug: like a me-too drug, this is similar to one already developed but in this case it has been developed by the same company.

Me-too drug: a compound which is structurally related to a known compound and which contains only minor pharmacological and chemical differences. There are many examples of me-too drugs for example the family of anti-ulcer H₂ blockers which includes cimetidine, ranitidine and famotidine. The diagram below shows their structures and structural similarities in blue. Cimetidine was first to enter the market in about 1976 followed by ranitidine in about 1981 then famotidine in 1985. They are all used to treat peptic ulcers.



Mean residence time (MRT): the average time a drug remains in the body after a single dose has been given. MRT is expressed as area under the first moment vs time curve divided by the area under the concentration vs time curve.

Mebendazole: a broad-spectrum benzimidazole antihelminthic compound used to treat threadworm, roundworm, whip worm and hookworm infections in humans and against lungworms in horses, cats and dogs in addition. Mebendazole is also used to treat trichinosis (a gastrointestinal worm infection) particularly at the muscular stage of Trichinella spiralis in animals.

Mecamylamine: a nicotinic receptor antagonist used to treat hypertension. It is being investigated as therapy to help quit smoking.

Mechanogated membrane ion channels: also known as mechanosensitive (MS) ion channels, ion channels which are activated by mechanical forces rather than chemical agonists.
Hamill OP and McBride DW. The pharmacology of mechanogated membrane ion channels. Pharmacological Reviews (1996) Vol 48; 231-252

Mechanogated ion channel blockers: compounds blocking mechanogated membrane ion channels. Examples include gadolinium, amiloride and gentamicin.

MED: minimum effective dose

Median effective dose (ED₅₀): the dose of a drug required to illicit 50% of the maximum possible effect.

Median lethal dose (LD₅₀): the dose of a drug found to cause deaths in 50% of a population of test animals.

Mediator: any compounds which can illicit or help illicit an inflammatory or allergic response. Examples include prostaglandins, histamine and serotonin.

Meglitinides: a group of drugs used to treat type 2 (non-insulin-dependent diabetes). Examples include nateglinide and repaglinide. They are non-sulphonylureal insulin secretagogues which lower blood sugar levels by increasing the release of insulin from the pancreas.

Melanin- concentrating hormone (MCH): a 19 amino acid cyclic peptide mainly expressed in the hypothalamus and implicated in the control of general arousal and goal-orientated behaviour in mammals. It also appears to play an essential role in the regulation of food intake. It is an orexigenic (ie increases appetite and food intake) hypothalamic neuropeptide. MCH is synthesized primarily in the lateral hypothalamus and zona incerta.

Melanin- concentrating hormone receptors (MCHR): receptors for melanin-concentrating hormone of which two are currently known, ie hMCH-1R and hMCH-2R, for which MCH is a natural ligand. They are implicated in the control of feeding behaviour.

Melanin- concentrating hormone (MCH) antagonists: compounds which block the effects of melanin-concentrating hormone and so suppress appetite. They are being developed for the treatment of obesity and include SNAP-7941, NBI-1A and NBI-1B.

Melanocortins (MC): a group of endogenous peptides which include α-melanocyte-stimulating hormone (α-MSH and also known as α-melanotropin), β-MSH and γ-MSH and adrenocorticotrophic hormone (ACTH). They are derived from the pro-opiomelanocortin gene and the melanocortins have important physiological functions in energy balance, sexual function, pigmentation and inflammation. The melanocortin system is responsible for the maintenance of energy balance via the regulation of both food intake and energy expenditure.

Melanocortin receptors: a family of G protein-coupled receptors (GPCRs) of which five are currently known, MC₁, MC₂, MC₃, MC₄ and MC_5, and for which melanocortins are the natural ligands.

Melanocyte stimulating hormones (MSH): also known as intermedins, peptide hormones produced in cells in the intermediate lobe of the hypothalamus. Three are known , α-MSH (melanotropin), β-MSH and γ-MSH. They stimulate the synthesis and release of melanin by melanocytes (they are melanogenic) and play a role in appetite and sexual function.

Melanocyte- stimulating hormone antagonists: compounds which antagonize the effects of melanocyte-stimulating hormone. Examples include the agouti protein and Met-Pro-D-Phe-Arg-D-Trp-Phe-Lys-Pro-Val-NH₂. They are of potential use in increasing food intake.

Melanotropin: also known as α-melanocyte stimulating hormone (α-MSH) .

Melatonin: a pineal gland hormone (N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide) first isolated around 1958 which was found to be primarily synthesized in a circadian manner with peak secretion occurring during nighttime. It has endocrinological, neurophysiological and behavioural functions and is the subject of research into disordered circadian rhythms seen in sleep disorders in the elderly and in shift workers and in jet-lag. Melatonin shows a wide species difference in its binding sites and binds to specific receptors in the suprachiasmatic nucleus in the hypothalamus. Melatonin is synthesized from the dietary amino acid L-tryptophan which is converted to 5-hydroxytryptophan from which 5-hydroxytryptamine (5-HT) is made. 5-HT is converted to melatonin in a two-step process mainly in the pineal gland. Melatonin has been used in veterinary medicine to control oestrus.

Melatonin receptors: G protein-coupled receptors for the peptide hormone melatonin. Three are currently known, ie MT_1, MT₂ and MT_3.  They mediate the effects of melatonin, ie they control sleep.

Melphalan: an alkylating agent and anticancer agent used clinically to treat multiple myleoma, advanced ovarian adenocarcinoma, advanced breast cancer, childhood neuroblastoma and polycythaemia vera (excess production of erythrocytes as a result of a proliferative abnormality). Melphalan is also used to treat multiple myelomas in cats and dogs.

Memantine: a drug used to treat moderate to severe dementia in Alzheimer's disease. It is a potent NMDA receptor antagonist which inhibits glutamate transmission in the brain. It binds to the NMDA-operated cation channels and blocks this ion channel. It does not induce psychotropic effects or memory impairment and has 5-HT₃ antagonist actions. Memantine is also a dopamine-releasing drug.

Membrane labilizers: compounds which make membranes less stable. Examples include veratridine and retinol.

Membrane stabilizer: compounds which make membranes more stable. Examples include citicoline (cytidine-5-diphosphocholine; CDP-choline) which is a naturally occurring nucleotide derivative. It may reduce central nervous system ischaemic injury by stabilizing cell membranes and may also reduce free radical generation. Polaxymer 188 may be of use in treating muscular dystrophy.

Membrane stabilizing action (MSA): a property observed with a variety of drugs such as β-blockers such as propranolol and acebutolol. This action may be beneficial in protection against posthypoxic cardiac contractile abnormalities and metabolic disturbances.

Membrane transporter: a carrier-mediated, energy-consuming system to transport molecules such as water-soluble vitamins, organic cations, amino acids, dipeptides, monosaccharides, monocarboxylic acids, phosphates and nucleosides into cells.
Lee VH. Membrane transporters. Eur J Pharm Sci (2000) 11 (2); S41-50

Meperidine: a synthetic opioid agonist similar in structure to atropine with morphine-like actions. It is used to treat moderate to severe pain in humans and animals and as a pre-anaesthetic in animals. It acts primarily on μ-opioid receptors and has a weak atropine-like action on muscarinic receptors.

Mephenesin: an aromatic ether and centrally acting muscle relaxant. It acts by selectively inhibiting polysynaptic excitation of motor neurones although its mechanism of cellular action is unclear.

Meprobamate: a drug introduced in the mid 1950s for the short-term treatment of anxiety but which is less effective than benzodiazepines, more hazardous if overdosed and more prone to induce dependence. It acts at multiple sites in the central nervous system including sites in the thalamus and limbic system although its mechanism of action is not fully understood. Carisoprodol (a muscle relaxant) is a prodrug of meprobamate.
Ramchandani D et al. Meprobamate-tranquilizer or anxiolytic? A historical perspective. Psychiatr Q (2006) Spring 77(1);43-53

Mepyramine: a selective H₁ histamine receptor inverse agonist (it also has antagonist effects) which has been used to treat skin inflammation such as nettle rash in the form of a topical cream.

Mercaptoethylguanidine sodium succinate: also known as MEG sodium succinate, a selective inhibitor of inducible nitric oxide synthase (iNOS) and a peroxynitrite scavenger. This compound may also inhibit cyclooxygenase.

6- Mercaptopurine: a metabolite of azathioprine and a cytotoxic immunosuppressant used clinically to treat acute leukaemias and inflammatory bowel disease. It is a purine antimetabolite first synthesized in 1952. Although its exact mechanism of action is unclear, it is first converted by hypoxanthine guanine phosphoribosylpyrophosphate to a thiol nucleotide form which is known to be cytotoxic. The cytotoxicity of 6-mercaptopurine appears to be due to interference with de novo purine biosynthesis, inhibition of RNA synthesis and incorporation into DNA during S phase of the cell cycle leading to deformation of DNA.

MES: maximal electroshock seizure

Mescaline: a hallucinogen and recreational and psychadelic drug. It is the main active component of peyote and is present in the peyote cactus.

Mesenteric window angiogenesis assay: a model of angiogenesis used to investigate the effect of drugs on neovascularization.
Norrby K. On the quantitative rat mesenteric-window angiogenesis assay. EXS (1992) 61;282-6

Meso compounds: stereoisomers which occur when a molecule has two chiral centers and each chiral center has identical substituents on it. Examples include tartaric acid.

Mesolimbic- mesocortical pathway: a neuronal pathway involved in schizophrenia as there is excessive dopamine neuronal activity in this pathway in schizophrenia patients. There are four major dopaminergic systems in the brain, ie the mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular pathways. It is known that drugs of abuse induce the release of dopamine in the mesolimbic-mesocortical pathway. It is sometimes referred to as the pleasure pathway.

Mesylate: a salt or ester of methanesulphonic acid. Examples of mesylates used in clinical medicine include doxazosin mesylate (used to treat hypertension and benign prostatic hyperplasia), imatinib mesylate (used in myeloid leukaemia) and saquinavir mesylate (used in retroviral infections).

Meta-analysis: also referred to as overview analysis, a statistical method of combining data obtained from different experiments or trials, providing certain criteria applicable to each trial are met, which provides greater power and significance of the overall results.

Metabolic cage: cages used to house experimental animals and which allow the separation and collection of urine and faeces so that they may be analysed for the presence of drugs and/or their metabolites.

Metabolism (of drugs): also referred to as biotransformation, the process of detoxifying a drug usually in the liver and preparing it for excretion from the body. The main reactions involved are divided into two phases:
Phase I: oxidation, reduction or hydrolysis. The products of these reactions are often more potent or more toxic than the parent compounds. In Phase I reactions the product usually becomes less lipid soluble, more water soluble and more readily excretable through the kidneys and, as they are often more polar, helps prevent reabsorption by the kidney tubules. Examples of drugs undergoing Phase I reactions include pentobarbital (oxidation), nicotine (N-acetylation), amphetamine (deamination) and thiopental (desulphuration).
Phase II: conjugations. Again taking place mainly in the liver, these reactions link, for example, a glucuronide to the parent molecule of the product of a Phase I reaction. Products of conjugations have greater water solubility than their parents compounds and are readily excreted through the kidneys. Examples of compounds undergoing Phase II metabolism include morphine (glucuronidation), sulphonamides (acetylation), catecholamines (sulphate conjugation) and histamine (methylation).

Metabolomics: the study of the metabolites of specific cellular processes. The metabolome is a collective term all the metabolites including primary and secondary metabolites, hormones and other signalling molecules in an organism and so is indicative of the end products of its gene expression.
Nordström A, Lewensohn R. Metabolomics: Moving to the Clinic. J Neuroimmune Pharmacol (2009) Apr 28

Metabotropic receptors: one of the major classifications of neurotransmitter receptors (the other being inotropic). Metabotropic receptors are monomeric proteins with seven transmembrane domains indirectly linked to ion-channels on the cell plasma membrane via a signal transduction mechanism. This class of receptor includes receptors for metabotropic glutamate receptors, muscarinic receptors, GABA_B receptors, most serotonin receptors, catecholamine receptors, histamine receptors and neuropeptide receptors. Activation of these receptors can both open and close ion channels.

Metalloproteases (matrix metalloproteases, MMP): also known as matrixins, a family of about 20 enzymes which bind metals such as zinc and calcium in the active site and which are proteases. They play important roles in tumour metastasis, embryonic development, wound healing and matrix degradation. The particularly affect tissue remodelling where collagen and proteoglycans are present and are important targets for drugs being developed to inhibit metastasis and connective tissue disorders.

Metalloprotease inhibitors: compounds which inhibit the destructive effects of metalloproteases on the extracellular matrix and which are being developed to treat inflammation, connective tissue disease and to inhibit metastasis. Examples include Ro32-3555 (Trocade), a collagenase selective inhibitor.

Metanephrine: a metabolite of adrenaline (epinephrine) and usually found in the blood when there is phaeochromocytoma (a usually benign tumour of the adrenal medulla which secretes catecholamines) present.

Metastasis: a process where tumour cells are released or break off from a primary tumour mass, pass through the body in the blood or lymphatic tissue and then establish themselves in a secondary site and grow like the primary tumour. Tumours developing in this way can be as lethal as primary tumours.

Metastasis inhibitor: compounds which inhibit the spread and establishment of metastatic tumours in parts of the body other than that in which the primary tumour is present. Metastasis inhibitors act by a variety of mechanisms including inhibition of attachment of metastatic cells for example by integrin inhibitors and cimetidine which inhibits the expression of E-selectin on the surface of endothelial cells, proteolysis of the matrix membrane for example by collagenase modulators and inhibition of metastatic growth for example by interleukin antagonists or TGF-β antagonists.

Metformin: a biguanide hypoglycaemic compound used clinically to treat diabetes. It inhibits gluconeogenesis and increases peripheral utilization of glucose. It only works in the presence of insulin so requires the presence of some functional β-cells in the islets of Langerhans in the pancreas.

Methacholine: a muscarinic receptor agonist similar in structure to acetylcholine but with a methyl group in the β position of choline. It is a weak nicotinic receptor agonist too and is hydrolysed by acetylcholinesterase although more slowly than acetylcholine. It has no clinical uses in humans.

Methadone: a synthetic opioid agonist used clinically to treat opioid dependence, severe pain and cough in terminal disease. It is structurally and pharmacologically similar to morphine but longer acting. Its use in the treatment of opioid dependence relies on its morphine-like effects but it shows little euphoric effect.

Methamphetamine: a neurotoxin and an addictive stimulant drug which is chemically related to amphetamine but which has more potent effect on the central nervous system. Methamphetamine increases energy (it is a locomotor stimulant) and alertness levels and decreases appetite and, like amphetamine, has anorectic actions (ie, it promotes weight loss due to decreased food intake).
Methamphetamine is a drug of abuse and is otherwise known as speed, meth and chalk and methamphetamine hydrochloride (which looks like ice in its crystal form) is known as ice, crystal, glass and tina.

Methamphetamine- induced behavioral sensitization: an animal model used to determine vulnerability of relapse of schizophrenia. In this model, repeated administration of low doses of methamphetamine (or a similar CNS stimulant such as amphetamine) to rodents causes progressive augmentation of locomotor activity and this is referred to as behavioral sensitization.

Methamphetamine- induced hyperkinesia: a form of methamphetamine-induced motor disturbance in which repeated administration of low doses of methamphetamine lead to hyperkinesia. It has been used as an animal model to test drugs.

Methamphetamine- induced place preference: also known as methamphetamine-induced conditioned place preference, an animal model in which repeated administration of low doses of methamphetamine cause a dose-dependent place preference.

Methapyrilene: an antihistamine found in cold and flu remedies and used to treat allergies.It is also known to be a hepatotoxicant and a nongenotoxic hepatocarcinogen used as a pharmacological tool to induce lived tumors and liver damage.

Methaqualone: an addictive, sedative hypnotic once used as a hypnotic to treat insomnia. It is a drug of abuse. It was marketed in 1965 in the US under the name Quaalude.

Methicillin: a semisynthetic penicillin and narrow-spectrum β-lactam antibiotic used clinically to treat bacterial infections. It is resistant to β-lactamases (also known as penicillinases) but resistance to it by organisms such Staphylococcus aureus is a clinical problem so is not a drug of choice.

Methicillin- resistant coagulase negative staphylococci (MRCNS): strains of staphylococci which have become resistant to the antibiotic effects of methicillin largely because they produce a penicillin-binding protein which neutralizes the effects of methicillin. MRCNS is found in humans, livestock and companion animals and has limited the use of methicillin as an antibiotic.

Methicillin- resistant staphylococcus aureus (MRSA): a strain of Staphylococcus aureus which has become resistant to the effect of methicillin due to the production of altered penicillin-binding protein following the acquisition of the mecA gene. This binding protein cannot bind β-lactams and they have no effect on cell wall synthesis. MRSA emerged as far back as 1961 in the UK and has caused many deaths worldwide since.

Methimazole: 1-methylimidazole-2-thiol, a thioureylene and antithyroid drug used clinically to treat Grave's disease (a form of hyperthyroidism). Methimazole acts by inhibiting the synthesis of thyroid hormone probably by inhibiting the iodination of tyrosyl residues in thyroglobulin and may competitively inhibit thyroperoxidase-catalysed oxidation by acting as a substrate for this enzyme.

Methoctramine: a cardioselective M₂ muscarinic receptor antagonist used as a pharmacological tool. It directly inhibits the high affinity GTPase activity of G proteins and it may improve memory.

Methohexital: a barbiturate derivative used as a short-acting, rapid onset sedative for anaesthesia. Like other barbiturates, it binds to a distinct site which is associated with GABA_A receptors.

Methonium compounds: compounds containing polymethylene bis-trimethylammonium cations which are generally ganglionic blockers and depolarizing muscle relaxants. Examples include decamethonium.

Methotrexate: previously known as amethopterin, a folic acid analogue, an anticancer and antimetabolite inhibitor of dihydrofolate reductase (an enzyme essential in DNA synthesis) used clinically as maintenance therapy for childhood acute lymphoblastic leukaemia and for choriocarcinoma, non-Hodgkin's lymphoma and a number of other solid tumours. It is also used in uncontrolled psoriasis and in moderate to severe active rheumatoid arthritis. Methotrexate is used in cats and dogs to treat lymphomas, carcinomas, sarcomas and transmissible venereal tumours.
It competitively and reversibly inhibits DNA synthesis because it is similar in structure to folic acid which is the natural substrates for dihydrofolate reductase. It prevents the conversion of folic acid to dihydrofolate and then to tetrahydrofolate. (Tetrahydrofolate is normally then converted to N⁵,N¹⁰-methylenetetrahydrofolate which acts as a methyl group donor in various chemical pathways including the synthesis of deoxythymidine monophosphate which is required in the synthesis of thymidine.) Methotrexate is most effective in S phase of the cell cycle when purines, pyrimidines and DNA are being actively synthesized in the cell.



Methoxamine: a non-selective α₁-adrenoceptor agonist which causes a rise in blood pressure by vasoconstriction. It has been used to treat hypotension.

5-Methoxy-N- cyclopropanoyltryptamine: a potent melatonin receptor agonist. It is used as a pharmacological tool to investigate melatonin receptor subtypes.

Methoxyflurane: a halogenated ether and potent inhalational anaesthetic used which was once used for surgery but which is no longer used in humans. It has been used in veterinary medicine since about 1960 and is still used as an anaesthetic in cats and dogs usually as a maintenance anaesthetic after induction of anaesthesia by, for example, pentobarbital.

N-methyl-D- aspartate (NMDA): an endogenous glutamate analogue and natural agonist of N-methyl-D- aspartate receptors.

N-methyl-D- aspartate receptors (NMDAR): a class of endogenous ionotropic glutamate receptor which are sensitive to N-methyl-D-aspartate, glutamate and glycine (which acts as a co-agonist at NMDA receptor sites). They are important in excitotoxicity and neuronal plasticity in the brain.
These receptors are composed of NR1 and NR2 subunits and the glutamate binding domain is formed at the junction of NR1 and NR2 subunits. The glycine binding site is on NR1 an glycine binding is essential for the function of these receptors. Activation of NMDA receptors causes the opening of an ion channel without selectivity for cations and allows the flow of Na⁺, K⁺ and (to a lesser extent) Ca²⁺ ions across neuronal membranes.
Danysz and Parsons. Glycine and N-Methyl-D-Aspartate Receptors: Physiological Significance and Possible Therapeutic Applications. Pharmacological reviews. (1988) 50, Issue 4; 597-664
http://pharmrev.aspetjournals.org/cgi/content/full/50/4/597

N-methyl-D- aspartate receptor agonists: compounds which activate NMDA receptors, a process which normally requires the binding of glutamate and glycine to the receptor. Examples include N-methyl-D-aspartate and homoquinolinic acid.

N-methyl-D- aspartate receptor antagonists: compounds which block NMDA receptors and so inhibit . Examples include ketamine, dextromethorphan, amantadine and phencyclidine, MK-801and memantine (which is used clinically to treat moderate to severs Alzheimer's disease).

NMDA receptor glycine site antagonists: compounds which specifically block the glycine binding site of the NMDA receptor. Examples include L-701,324, L-689,560 and GV96771A. They may be of use in the treatment of Parkinson's disease.

Methylazoxymethanolacetate (MAMA): a short-acting, anti-mitotic which has been used as a pharmacological tool as it is a potent carcinogen and neurotoxin. It inhibits hepatic DNA, RNA, and protein synthesis.

3-Methylcholanthrene: a carcinogen and pharmacological tool used to study the effects of anticancer compounds.

Methyldopa: a catecholamine (3,4-dihydroxyphenyl)-2-methyalanine) analogue of levodopa.. It is an α-2 adrenergic agonist which has both central and peripheral nervous effects. It is used clinically as an antihypertensive agent where it produces its effects centrally.
   Methyldopa is taken up by adrenergic neurons and converted by dopa decarboxylase then dopamine β-monooxygenase to α-methylnoradrenaline which is a false transmitter. This compound accumulates and displaces noradrenaline from storage vesicles. It is released along with noradrenaline is normal neuronal activity but is less potent as a transmitter postsynaptically but does activate presynaptic α₂ adrenoceptors leading to feedback inhibition and lower transmitter release.

Methylergonovine: also known as ergometrine and methergine, a semi-synthetic ergot alkaloid which is used to prevent or treat bleeding from the uterus following childbirth or abortion due to its vasoconstrictor actions. It also has effects similar to LSD to which it is structurally related when given at higher doses than used therapeutically.

3-Methylfentanyl: also known as China White, a designer drug (ie, one which is for recreational use but which is a derivative of an approved drug or an illegal drug so as to circumvent existing legal restrictions or increase activity or both). It is a potent narcotic analgesic and the cis-isomer is approximately 1000 or more times more potent than morphine.

N-Methylnitrosourea (MNU): a carcinogen and pharmacological tool used to induce experimental tumours. Typically, intrarectal doses of 2mg N-methylnitrosourea dissolved in 0.5ml water given three times a week for 4-5 weeks will induce colon cancer.

α-Methyltyrosine: a tyrosine analogue and an inhibitor of tyrosine 3-monooxygenase and which inhibits the synthesis of all catecholamines. It has been used to control excessive sympathetic stimulation caused by adrenaline and noradrenaline released from phaeochromocytoma (a largely benign tumour of the adrenal medulla which causes the release of adrenaline and noradrenaline into the blood).

5-Methylurapidil: a selective α_1A-adrenoceptor antagonist used as a pharmacological tool to investigate adrenoceptor subtypes. Urapidil has been used as an antihypertensive as it is a vasodilator.

Methyllycaconitine: a toxin purified from the seeds of Delphinium brownii and a selective and potent antagonist of α7 neuronal nicotine receptors. It is used as a pharmacological tool to investigate nicotinic receptor subtypes.

Methylphenidate: an amphetamine-like CNS stimulant used clinically to treat attention deficit hyperactivity disorder (ADHD). It has also been used to treat traumatic brain injury, daytime sleepiness and chronic fatigue syndrome. Methylphenidate is a dopamine reuptake inhibitor although the exact mechanism of its actions in ADHD are unclear. See http://en.wikipedia.org/wiki/Methylphenidate

Methysergide: a synthetic ergot alkaloid and LSD-like drug used clinically to prevent severe recurrent migraine, cluster headaches and other vascular headaches in patients who do not respond to other treatment. It is not a drug of choice due to its side effects. It is structurally related to the oxytocic agent methylergonovine and is a more potent peripheral serotonin receptor antagonist than other ergot alkaloids. Methysergide blocks 5-HT receptors in the brain and is a weak vasoconstrictor.

Metirosine: a compound (α-methyl-L-tyrosine) which inhibits tyrosine carboxylase and prevents the conversion of tyrosine to dopa. Treatment of neurones with this compound will lead to a depletion of transmitter stores in noradrenergic and dopaminergic neurones and chromaffin cells. It is used clinically in the pre-operative management of phaeochromocytoma and in the long term to treat this disorders where surgery is unsuitable.

Metoclopramide: an anti-emetic drug used to clinically to treat nausea and vomiting particularly those related to gastrointestinal diseases and those caused by treatment cytotoxic anticancer drugs or radiotherapy. It is also used to relieve the symptoms of nausea associated with migraine attacks.
Metoclopramide is a dopamine receptor antagonist which exerts its actions in the chemoreceptor trigger zone in the area postrema in the brain. It also directly stimulates the motility of the stomach and intestines. This increases the gastric emptying rate but without a concomitant increase in gastric acid secretion. Metoclopramide is also used clinically to treat non-ulcer dyspepsia and in the treatment of gastro-oesophageal reflux disease (GERD).

Metoprolol: a cardioselective but not cardiospecific β₁-adrenoceptor antagonist used clinically to treat hypertension, angina and arrhythmias.

Metrazole: a non-competitive GABA antagonist which acts as a CNS stimulant of respiration. It can induce seizures in small animals and has been used as a pharmacological tool in the anti-metrazole seizure (threshold) test to evaluate the effects of anticonvulsants.

Metronidazole: a nitroimidazole amoebicidal compound used clinically to treat amoebal infections in humans and small animals. It is effective against Entamoeba histolytica, giardiasis such as that caused by Giardia lamblia, trichomoniasis such as that caused by Trichomonas vaginalis, ulcerative gingivitis and Crohn's disease. It is the drug of choice in the treatment of acute invasive amoebic dysentery. Metronidazole appears to act against trophozoites of Entamoeba by damaging the DNA of the infective organism by the production of toxic oxygen products of this drug by the parasite itself.Examples of nitroimidazole amoebicidals are shown in the figure below with the nitroimidazole moiety shown in blue.



Metyrapone: a competitive inhibitor of 11β-hydroxylation (it is an 11 β-hydroxylase inhibitor) in the adrenal cortex and so inhibits the production of cortisol and to a lesser extent aldosterone. This decrease in cortisol leads to an increase in the synthesis of adrenocorticotrophic hormone (ACTH) which leads to an increase in the production of cortisol precursors. Metyrapone is used to evaluate the function of the anterior pituitary and to treat Cushing's syndrome (an endocrine disorder caused by high levels of cortisol in the blood).

Meyer-Overton hypothesis: a hypothesis about anaesthetics which says that the minimum alveolar concentration (MAC) of a volatile substance is inversely proportional to its lipid solubility. The more lipid soluble the anaesthetic, the higher the potency and the lower the MAC.

MgTX: margatoxin

Mianserin: an atypical and tricyclic antidepressant.used clinically to treat depressive illness particularly where sedation is required. Mianserin blocks α₂-adrenoreceptors, 5-HT₂ serotonin receptors and H₁ histamine receptors. It does not affect monoamine reuptake. It may increase noradrenaline release by blocking α₂ adrenoceptors on adrenergic neurones.

MIC: minimum inhibitory concentration.

Michaelis-Menten equation: also known as the Henri-Michaelis-Menten equation, one of the best and earliest known theoretical descriptions of enzyme reaction kinetics.

Miconazole: an azole and antifungal compound used topically and orally to treat fungal infections such as oral and intestinal infections and to treat wounds infected with fungi. Azoles including miconazole, ketoconazole, fluconazole and itraconazole inhibit fungal P450 enzymes which are responsible for the synthesis of ergosterol, the main sterol and an important structural component of fungal cell walls. The azoles inhibit fungal replication.

Microfilaricide: compounds which kill microfilaria, the immature forms heartworms which circulate in the blood. In humans, filarial infections can cause river blindness (onchocerciasis) and elephantiasis (caused by the nematode worms Wuchereria bancrofti and Brugia malayi in the lymphatic system). These can be treated with diethylcarbamazine, albendazole and ivermectin.
Examples of veterinary microfilaricides include dithiazanine iodide, ivermectin, levamisole, milbemycin and fenthion. Macrofilaricides are drugs which kill adult filarial worms (macrofilariae). An example of a veterinary macrofilaricide is moxidectin.

Micronucleus test: an in vivo test to determine if a compound has clastogenic effects (ie, it causes chromosome breaks) or impairs mitosis, spindle fibre function or cytokinesis. These tests are usually carried out using mice and the effects of these compounds are observed by histological examination of erythrocyte stem cells taken from treated animals. Micronuclei in these cells indicates that chromosomes or their fragments have failed to migrate properly in anaphase.

Micropig^®: the registered trade name of a small, docile pig originating in the Yucatan peninsula in Mexico. This predominantly hairless, slate grey to black pig is used as an alternative to dogs and primates in cardiovascular studies since body weight does not usually exceed about 16-18kg at one year of age. It is therefore relatively economical to rear. It does show some cardiac anomalies such as arrhythmias compared to dogs and primates but is otherwise a suitable small animal for cardiovascular studies. Hairless micropigs have been used to model skin disease.

Microsomal triglyceride transfer protein (MTTP): a heterodimeric lipid transfer protein which catalyzes the transport of triglycerides, cholesteryl esters and phosphatidylcholine between membranes. MTTP is a target for the control of lipid metabolism.

Microsomal triglyceride transfer protein (MTTP) inhibitors: compounds which inhibit MTTP and so decrease blood triglyceride levels. They are being developed to treat hyperlipidemia and examples include JTT-130, implitapide and CP-346086.

Microsomes: small enclosed vesicles about 100nm in diameter which are membrane fragments formed form the endoplasmic reticulum when cells are homogenized.

Midkine: a basic protein strongly expressed in midgestation which promotes the survival and migration of various cells but also promotes growth of fibroblasts and tumour cells, it promotes the survival of embryonic neurons, promotes the migration fo neurons and neutrophils and promotes angiogenesis in tumours. See http://www.midkine.org/index-e.html

Mifepristone (RU486): an anti-progestogenic steroid and partial progesterone agonist but which inhibits the actions of its progestogen. It sensitizes the myometrium to prostaglandin-induced contractions and it dilates and softens the cervix. It is used clinically in combination with vaginal administration of the prostaglandin gemeprost (about 48 hours later) for medical termination of pregnancy.
Mahajan DK, London SN. Mifepristone (RU486): a review. Fertil Steril (1997) Dec 68(6):967-76

Migraine-abortive agent: compounds which stop acute migraine attacks. Examples include tolfenamic acid, triptans (5-HT₁ serotonin agonists such as almotriptan, sumatriptan and zolmitriptan) and ergotamine derivatives eg, ergotamine tartrate although these are rarely used now.

Mimetic: a substance that mimics or imitates the actions of another substance which usually has a well established physiological function. Examples include sympathomimetics and peptidomimetics.

Mineralocorticoids: corticosteroids produced by the adrenal cortex which are involved with Na⁺ and K⁺ balance and also in water balance within the body. The most important is aldosterone which causes Na⁺ (and therefore water) retention by the kidneys and K⁺ excretion.

Minimum alveolar concentration (MAC): a measure of the potency of an inhalational anaesthetic which is the alveolar concentration that prevents gross purposeful movement in 50% of patients or animals treated with it in response to a standardized and painful stimulus. See Meyer-Overton hypothesis.

Minimum inhibitory concentration (MIC): the minimum concentration of an antimicrobial compound in a given culture medium which inhibits the growth of the bacterium. The MIC of a particular antibiotic is given in mg/L and is an indication of susceptibility of bacteria and fungi to microbistatics and microbicides.

Minor tranquilizers: also known as anxiolytics, ataractics, neuroleptics and sedatives, drugs which are used to treat anxiety, to induce calm and treat sleep disorders but not psychoses such as schizophrenia for which major tranquilizers are used. Several types of compound are grouped into minor tranquilizers and include benzodiazepines, 5-HT_1A serotonin receptor agonists, barbiturates, β-adrenoceptor antagonists and other drugs such as choral hydrate, meprobromate and paraldehyde.

Minoxidil: a vasodilator used clinically to treat severe hypertension which is resistant to other drugs. It causes an increase in cardiac output and fluid retention so is usually used in conjunction with a diuretic and a β- blocker. When applied topically, minoxidil can promote hair growth and is used to treat male-pattern baldness. The mechanism by which it stimulates hair growth is unclear although it may be due to vasodilation and improved blood flow around the hair follicles.

Miotics: drugs which cause constriction of the pupil (miosis) and increased drainage of the aqueous fluid in the eye. They are used to treat glaucoma because they can open drainage channels in the trabecular meshwork closure of which is caused by contraction or spasm of the ciliary muscles. Examples of miotics include parasympathomimetics and cholinergic agonists such as acetylcholine chloride, pilocarpine and carbachol.

Misoprostol: a synthetic prostaglandin analogue which has gastroprotectant and antisecretory properties and which is used clinically to treat benign gastric anc duodenal ulcers and NSAID-associated ulcers. It is also used in formulations with diclofenac or naproxen.
   Misoprostol is also used by oral or vaginal administration to induce abortion often with mifepristone. In this case, mifepristone blocks the effects of progesterone which is needed to maintain pregnancy, the uterine lining begins to shed and the cervix begins to soften. A follow up dose of misoprostol causes the uterus to contract and the foetus is usually expelled within 6 to 8 hours.

Miticides: also known as acaricides.

Mitogen-activated protein kinase (MAP kinase): see MAP kinase.

Mitomycins: a family of antibiotic and anticancer compounds (they are cytotoxic antibiotics) based around a pyrro[1,2-a]indole nucleus and produced by some strains of Streptomyces such as Streptomyces verticillatus and Streptomyces caespitosus. They were discovered in the 1950s (mitomycins A and B) and showed potent antibacterial activity, moderate antitumor actions but were quite toxic. Mitomycin C was isolated from Streptomyces caespitosus in 1958.
Mitomycin C is used clinically in the treatment of upper gastrointestinal, bladder and breast cancer. It is activated in vivo to a bifunctional or trufunctional compound which binds to (preferably) the guanine and cytosine moieties in DNA leading to crosslinking and inhibition of DNA synthesis and function.

Mitosis inhibitors: compounds which inhibit mitosis (non-sex cell division) and which are used to treat tumours. Examples include vinca alkaloids such as vincristine and vinblastine. They bind to tubulin protein in the mitotic spindle and block its polymerization to form microtubules so blocking cell division in metaphase.

MK 912: an α₂-adrenoceptor antagonist used as a pharmacological tool in the study of adrenoceptor subtypes.

MMOA: multiple mechanisms of action

MMP: matrix metalloprotease.

Mofetil: a 2-morpholinoethyl ester. Examples include mycophenolate mofetil used as an immunosuppressant.

Molal: a one molal solution contains one mole of substance in 1000g of solvent.

Molarity (M): a measure of the concentration of a solution of drug or other substance. A 1M (one molar) solution contains 1 mole (ie, Avogadro's number, 6.022 x 10²³, of molecules) of a drug in 1000mL  of solution.
Normal (N) has been used as a measure of the strength of acids and bases but this term is outdated and molarity is preferred.

Mongolian gerbil: a commercially available laboratory animal originally from a litter caught in Mongolia in the 1930s. These animals are subject to a variety of spontaneous conditions such as epileptiform seizures, hyperadrenocorticism, diabetes, obesity, periodontal disease and dental caries.

Monoamines: small organic molecule containing both a carboxyl group and an amino group bonded to the same carbon atom. They are abundant in humans and include (the biogenic monoamines) adrenaline, noradrenaline, histamine, serotonin and dopamine.

Monoamine oxidase (MAO): officially known as amine oxidase (EC 1.4.3.4), an enzyme which catalyze the oxidative deamination of catecholamines to form their aldehydes which (in the periphery) are further dehydrogenated by aldehyde dehydrogenase to form carboxylic acids or alcohols. MAO is bound to mitochondrial membranes and is abundant in noradrenergic nerve terminals and in other locations such as the liver and intestinal epithelium. MAO also oxidizes dopamine and 5-HT.
There are two known isozymes of MAO, MAO-A and MAO-B and they differ in their substrate preference. MAO-A prefers 5-HT and noradrenaline, whereas MAO-B is more common in human platelets and prefers more hydrophobic amines such as phenethylamine and benzylamine.

Monoamine oxidase inhibitor (MAOI): compounds which inhibit the actions of monoamine oxidases and so increase central and peripheral levels of catecholamines. They were introduced originally for the treatment of depressive illness. The first MAOI introduced were non-selective for MAO-A and MAO-B. The main problem with MAO-A inhibition is that dietary tyramine was not oxidatlvely deaminated by this enzyme in the gut allowing tyramine to enter the bloodstream. Tyramine is an indirectly acting sympathomimetic amine which has pressor effects in the blood vessels leading to the cheese reaction (ie, marked hypertension due to vasoconstriction). More MAO-B-selective compounds are used clinically to treat Parkinson's disease. Examples include selegiline (an irreversible suicide inhibitor of MAO-B) which is used alone or in combination with levodopa. Other MAO-B selective inhibitors include rasagiline, lazabemide and mofegiline.
   Older 1^st generation non-selective (and irreversible) MAOI include pargyline and tranylcypromine, phenelzine and isocarboxazid which are still used clinically to treat depressive illness. The 2^nd generation MAO-I which are irreversible but which show a preference for inhibition of MAO-B and include selegiline. Third generation MAOI include reversible inhibitors of monoamine oxidase (RIMA) such as moclobemide (an inhibitor of MAO-A but causing less pressor effects of tyramine). Moclobemide is used clinically to treat depressive illness and social phobia.
   Monoamine oxidase inhibitors are also used to treat demodectic, sarcoptic and notoedric mange (a skin disease in animals caused by mites) in dogs and cats. Examples include amitraz which disrupts the mite nervous system.

Monoamine reuptake inhibitors: compounds which inhibit the reuptake of monoamines and so potentiate the effects of monoamines on their receptors. They include dopamine reuptake inhibitors such as brasofensine, noradrenaline (specific) reuptake inhibitors (NRSI) such as amoxapine and maprotilene, (selective) serotonin reuptake inhibitors (SSRI) such as fluoxetine and sertraline, serotonin-noradrenaline reuptake inhibitors (SNRI) such as duloxetine and milnacipran and serotonin-noradrenaline-dopamine reuptake inhibitors.

Monoamine theory of depression: the idea that depressive illness arises from a deficit in noradrenaline and/or serotoninactivity in the brain and that antidepressants work by normalizing this deficit. It is based of the observation that monoamine oxidase inhibitors and tricyclic antidepressants both increase in the activity of monoamines in the brain and improve the symptoms of depression.

Monocarboxylate transporters: membrane transport proteins for monocarboxylate compounds such as pyruvate and lactate. They play an important role in energy metabolism and metabolite homeostasis.

Monochloramine: an ulcerogenic chloride of ammonia (NH₂Cl) used to induce (usually gastric) ulcers.

Monoclonal antibody: an antibody which has been derived from a single antibody-producing clone, ie all the antibodies produced by this clone are identical and have identical reactivity. These clones are actually myeloma cells which have been fused to antigen-sensitized spleen cells. The myeloma cells give the fused cell longevity and the spleen cell produces antibodies.
Monoclonal antibodies have a broad range of applications particularly in diagnostic medicine and therapy. Examples of MAb used in therapy include daclizumab and basiliximab in the treatment of transplant rejection, rituximab and bevacizumab in the treatment of cancer and infliximab and omalizumab in the treatment of inflammation. See http://en.wikipedia.org/wiki/Monoclonal_antibody

Monocrotaline: a pyrrolizidine alkaloid and a toxic plant constituent used to induce pulmonary hypertension in animal models. It causes pulmonary artery hypertension, right ventricular hypertrophy and pathological changes in the pulmonary vasculature. It has been used as a pharmacological tool to induce pulmonary artery hypertension and cardiac hypertrophy. It mechanism may be based on increasing oxidants, circulating levels of catecholamines and haemodynamic load or by inducing hypoxia in cardiac tissue.

Monolactams: also referred to as monobactams and monocyclic β-lactams, a class of β-lactams having only one ring in the structure and not the usual bicyclic structure associated with β-lactams. Examples include aztreonam.

L-N^G- Monomethyl arginine (LNMMA): a competitive nitric oxide synthase (NOS) inhibitor and an analogue of L-arginine. It inhibits NO production.

Monosodium glutamate-treated mouse: a mouse model of obesity and endocrinological dysfunction caused by the neurotoxic effects of monosodium glutamate (MSG) in the hypothalamus. Neonatal administration of monosodium glutamate permanently damages the neurons in the hypothalamic arcuate nucleus which contain growth hormone releasing hormone and prolactin-secretion inhibiting dopamine neuron cell bodies. These animals show obesity and stunted growth due to decreases in growth hormone levels.

Montelukast: a leukotriene receptor antagonist used to treat asthma and allergies. It blocks the actions of leukotriene D4 on cysteinyl leukotriene receptor CysLT₁ receptors in the bronchi causing bronchodilation. It is one of the 'leukast' family of anti-asthma drugs which includes pranlukast, zafirlukast, iralukast and cinalukast.

Mood stabilizers: also known as antimanics.

Morning-after pill: also knows as the post-coital pill, a form of contragestational agent which can prevent pregnancy which can be taken within 72 hrs of unprotected  intercourse to lessen the risk of conception. It is a pill containing levonorgestrel and increases the thickness of the natural mucus in the cervix making it difficult for sperm to cross from the vagina into the uterus. It also changes the lining of the uterus preventing it from being prepared for a fertilised egg. The morning after pill used to comprise two tablets which had to be taken twelve hours apart.

Morphinans: a family of morphine-like compounds which differ structurally from morphine with the absence the oxygen bridge. Morphinans are similar to morphine in the analgesic actions although they are often more potent and longer acting.



Morphine: a narcotic opioid analgesic used clinically as an antimotility agent (ie, it slows or halts peristalsis) to treat uncomplicated acute diarrhoea, to treat cough (it is an antitussive) and to treat moderate to severe pain of visceral origin eg, following surgery or that associated with cancer (often in palliative care). Morphine is an agonist of μ- opioid receptors and this receptor subtype is thought to be responsible for the analgesic actions of opioids

Morris hidden platform maze: a device used to test place learning and memory devised by Richard Morris in the mid 1980s. This device comprises a tank filled with water and a submerged (hidden) platform. The animal, usually a rat, is allowed to learn where the platform is and this method can be used to determine the effects of drugs on placed learning and memory.
Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods (1984) 11(1):47-60
See http://www.watermaze.org

Motilides: macrolides with direct contracting effects on the small intestine.
Itoh Z, Omura S. Motilide, a New Family of Macrolide Compounds Mimicing Motilin. Dig Dis Sci (1987) 32: 915

Motilin: a 22 amino acid gastroprokinetic polypeptide hormone produced and secreted from the endocrinocytes in the mucosa of the proximal small intestine. It plays an important role in the initiation of phase III activity of the interdigestive migrating contractions (IMC) in dogs and man and increases the production of pepsin.
In humans, the precursor of motilin consists of 115 amino acids including a 25 amino acid signal peptide and a 66 amino acid carboxy-terminal motilin-associated peptide (MAP). Motilin is abundant in the duodenum where it appears to act directly on motilin receptors located on gastrointestinal smooth muscle cells causing an increase in gut contractions and an increase in gastric emptying. Motilin receptors are also thought to be present in the nervous system.

Motilin receptor: a G protein-coupled receptor present in the gut to which motilin binds to cause increases gut activity.
Feighner SD et al. Receptor for motilin identified in the human gastrointestinal system. Science (1999) Vol. 284 No. 5423:2184 - 2188

Motilin receptor agonists: compounds which agonise motilin receptors and so increase gastric emptying rate. They are being developed to treat gastroparesis and gastroesophageal reflux disease (GERD). Examples include erythromycin A, the erythromycin derivative EM-523, GM611, KOS-2187 and ABT-229. They greatly increase gastrointestinal motor activity.

Motilin receptor antagonists: compounds which block the effects of motilin at its receptor site. Motilin antagonists are being developed for the treatment of irritable bowel syndrome (IBS) and functional dyspepsia. Slowing of the gut appears to inhibit the diarrhoea-like symptoms of IBS. Examples of motilin receptor antagonists include TZP-201, ANQ-11125, RWJ-68023.

Moxonidine: a second generation, centrally-acting antihypertensive which act as a selective I₁ imidazoline receptor agonist and an α₂-adrenoceptor agonist in the brainstem sympathetic nuclei. It is used clinically to treat mild to moderate essential hypertension and is similar to clonidine.

Mouse: a commonly used animal in research because it is easy to rear and inexpensive. A good source of genetic information about mice can be found at Mouse Genome Informatics (http://www.informatics.jax.org/).

Mouse ear-scratch reflex: also known as the scratch reflex, ear-scratch response and scratch-reflex stereotypy, a reflex in which the mouse scratches the head and area around the ear with the hind paw. It is observed after the administration of some types of hallucinogens such as the phenylisopropylamine, DOM and mescaline. Indolealkylamine hallucinogens, however, such as psilocybin do not illicit this reflex and LSD is essentially inactive. This reflex has been used to investigate the effects of some types of hallucinogens and psychoactive drugs in mice.

MPA: mycophenolic acid

MPPP: a designer drug (1-methyl-4-phenyl-4- proprionoxypiperidine) used for its opioid-like actions. (see MTPT).

MPTP: a neurotoxin (N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) which is structurally related to pethidine and which is used experimentally in models of Parkinson's disease. This compound appeared as a contaminant of MPPP which was a designer drug of abuse used in California in the early 1980s due to its opioid activity. MPTP is neurotoxic and is known to cause irreversible damage to dopaminergic fibers in the nigrostriatal pathway.

MRCNS: methicillin-resistant coagulase negative stsphylococci

MRSA: methicillin-resistant staphylococcus aureus

MRT: mean residence time

MSA: membrane stabilizing action

MT3 and MT7: toxins present in the venom of green mamba (Dendroaspis augusticeps). They are non-subtype selective muscarinic receptor antagonists.

MTTP: microsomal triglyceride transfer protein

MTT assay: a colourimetric cell proliferation inhibition assay carried out to determine the effect of compounds on cell proliferation such as in testing the effects of antimicrobial and anticancer drugs. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) is yellow and is oxidized to form purple formazan by mitochondrial reductases - the amount of formazan formed being directly related the number of cells (the colour can be measured spectroscopically). Antimicrobials and anticancer drugs decrease the formation of formazan (as dead cells cannot convert MTT to formazan) compared to untreated control cells (which can proliferate unimpaired).
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth (1983) 65:55-63

MTX: maurotoxin

Mucolytic: a drug which lowers the viscosity of mucus making it easier to expel from the airways. Mucolytics include agents that depolymerize the mucopolysaccharide-protein fibres in mucus. These agents are commonly used in the symptomatic treatment of coughs.

Multidrug resistance (MDR): a process where microorganisms and cells become resistant to the drug or drugs s being used to eradicate them despite being sensitive to these drugs at the start of treatment. There are several mechanisms by which cells can acquire multidrug resistance. Human P-glycoprotein (also known as MDR1 which normally expels toxins from cells) and the multidrug resistance-associated protein (MRP) both function as ATP-dependent cellular efflux transporters for cytotoxic drugs in human multidrug resistant cells. If they are overexpressed in tumours or cultured tissue cells, they expel the cytotoxic drug leading to resistance to these drugs. MDR is a common problem for the vinca alkaloids vincristine and vinblastine, dactinomycin and anthracyclines.

Multimeric receptors: receptors which are made up of more than one part. For example, ionotropic glutamate receptors are multimeric assemblies of four or five subunits and this is typified by GABA_A receptors.

Multidrug transporter: also known as P-glycoprotein, a transporter mechanism which evolved to protect cells from xenobiotics and is found in the cell membrane. The transporter is normally found in several key places in the body, specifically the lining the digestive tract where it reduces absorption of toxic compounds in the diet, in the kidney and liver where it helps in the excretion of xenobiotics and in the cells lining the capillaries in the brain forming one line of defense in the blood-brain barrier. In cancer cells, this transporter is responsible for resistance to anticancer compounds but can account for drug resistance in a broad range of mammalian, bacterial and fungal cells.
Mizutani T et al. Genuine functions of P-glycoprotein (ABCB1). Curr Drug Metab. 2008 Feb;9(2):167-74

Murad, Ferid (1936 - ): American pharmacologist who shared the Nobel Prize for Physiology or Medicine in 1988 with Furchgott and Ignarro 'for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system'.
http://nobelprize.org/nobel_prizes/medicine/laureates/1998/murad-autobio.html

Muramyl dipeptide (MDP): a nonspecific immunostimulant, the smallest immunologically active unit in the wall of a gram negative bacteria and an important component in its structure as it forms part of the peptidoglycan molecule (chemically it is N-acetylmuramyl-L-Ala-D-Glu-NH₂). It is an immunostimulant which can enhance nonspecific resistance to infection.
Traub S et al. MDP and other muropeptides--direct and synergistic effects on the immune system. J Endotoxin Res (2006), 12(2):69-85

Muricidal: relating to the killing of a rat or mouse and often applied to an unusual form of aggressive behaviour where a rat will kill and may partly eat a mouse.

Murine: usually taken as relating to rats and mice (but includes animals of the genus Muridae including rats, mice, gerbils and jirds).

Muropeptides: breakdown products of peptidoglycan from gram-positive and gram-negative bacteria and which have immunostimulant actions.

Muscarine: a toxic alkaloid obtained from the mushroom Amanita muscaria and some other fungi. It is a potent and selective mimic of acetylcholine at central muscarinic receptors. It also stimulates the peripheral parasympathetic system to induce miosis, vomiting, diarrhoea and bradycardia.

Muscarinic: relating to the actions of muscarine and the effects of compounds in agonizing or antagonizing muscarinic cholinoceptors.

Muscarinic receptors: also known as muscarinic cholinoceptor, membrane-bound acetylcholine receptors present in most tissues of which five have so far been identified, ie M₁, M₂, M₃, M₄ and M₅. They are metabotropic receptors and use G proteins in their signalling mechanism and have 7 transmembrane regions (in contrast to nicotinic cholinoceptors which are ion-gated). The table below shows the main classification of muscarinic receptors and some agonists and antagonists.

MP Caulfield and JM Birdsall. International Union of Pharmacology. Classification of Muscarinic Acetylcholine Receptors. Pharmacological Reviews. (1998) 50(2): 279-290
See http://pharmrev.aspetjournals.org/cgi/content/full/50/2/279.
Eglen RM, Watson N. Selective muscarinic receptor agonists and antagonists. Pharmacol Toxicol (1996) 78; 59-78

Muscarinic receptor agonist: compounds which agonize muscarinic receptors. They are used clinically for a range of disorders shown in the table above.

Muscarinic receptor antagonist: compounds which block muscarinic receptors. Their uses are shown in the table above.

Muscarinic toxins (MT): a family of peptides isolated from venom of green mamba (Dendroaspis angusticeps) black mamba (Dendroaspis polylepis). They fall into three groups, types A, B and C. Examples include MT3, MTx1 and MTx7. Muscarinic toxins show high affinity for muscarinic receptors and are used as pharmacological tool.

Muscimol: also known as agarin, pantherine and pyroibotenic acid, a psychoactive compounds (3-Hydroxy-5-aminomethylisoxazole) present in fly agaric (a mushroom, Amanita muscaria) and the deathcap mushroom (Amanita phalloides). It is the decarboxylation product of ibotenic acid and it is a selective GABA_A receptor agonist. It is used as a pharmacological tool to investigate these receptors.

Muscle relaxants: a diverse group of compounds used to induce the relaxation of smooth and skeletal muscles. There are broadly divided into five groups; 1) Non-depolarizing (also known as competitive neuromuscular blocking agents) and 2) depolarizing muscle relaxants are used clinically in anaesthesia as they relax the muscles of the trachea, diaphragm and abdomen. They also relax the vocal cords to facilitate intubation. 3) Centrally acting muscle relaxants and are used to treat chronic severe spasticity due to multiple sclerosis or traumatic section of the spinal cord. 4) Compounds acting directly on muscle to cause relaxation are used to treat chronic severe spasticity and malignant hyperthermia. 5) Other compounds.
1) Non-depolarizing muscle relaxants (ie the majority of these drugs) are also known as competitive muscle relaxants and compete with acetylcholine for nicotinic receptors in the muscle. This non-depolarizing group can be subdivided into the aminosteroid group which includes pancuronium, rocuronium, rapacuronium, pipecuronium and vecuronium and the benzylisoquinolinium group which includes atracurium, cisatracurium (a stereoisomer of atracurium), doxacurium and mivacurium. Other non-depolarizing compounds include gallamine, alcuronium, metocurine and fazadinium. All these compounds tend to have an intermediate to long duration of action and slow onset.
2) Depolarizing muscle relaxants induce a prolonged depolarization of the endplate of muscle fibres which leads to a loss of electrical excitability (hence the term depolarizing). They are not metabolized by acetylcholinesterase in the synaptic cleft so they remain in the cleft to continuously depolarize the end plate. They show rapid onset and short duration of action. Examples include suxamethonium, hexafluorenium and decamethonium.
The above two types of muscle relaxants are also known as parasympatholytics (they abolish parasympathetic effects on muscles) and are often classified by their duration of action as ultra-short acting (<15 minutes, eg succinylcholine, rapacuronium), short-acting (15-30 minutes, eg mivacurium), intermediate-acting (30-60 minutes, eg atracurium, cisatracurium, rocuronium and vecuronium) and long-acting (60-120 minutes or longer, eg pancuronium, gallamine, metocurine, doxacurium and pipecuronium).
3) Centrally acting muscle relaxants act via a central mechanism in the CNS and are used to treat muscle spasms such as those associated with tetanus and spasticity (characterized by hypertonicity which is an increase in normal muscle tone and resistance to stretching) and chronic severe spasticity associated with multiple sclerosis or traumatic spinal injury. They have various mechanisms of action. For example, baclofen is a selective  presynaptic GABA_B receptors agonist and it exerts its antispastic effects mainly in the spinal cord. Baclofen inhibits mono- and polysynaptic activation of motor neurons leading to a relaxation of muscle tone. Mephenesin acts mainly on the spinal cord inhibiting polysynaptic excitation of motor neurons. Guaifenesin is a centrally acting muscle relaxant used in combination with thiobarbiturates and ketamine in anaesthesia prior to surgery in horses, cattle and swine.
4) Compounds acting directly on muscle. These include dantrolene and quinine and musculotropic and neurotropic-musculotropic spasmolytics. Dantrolene is used to treat chronic severe spasticity of voluntary muscle and causes a decrease in muscle tone by interfering with the release of ionic calcium from the sarcoplasmic reticulum in muscle cells due to inhibition of ryanodine receptor (RYR) channels. Quinine has a curare-like effect on the motor endplate and directly reduces tone by altering the intracellular distribution of calcium. It is used to reduce the frequency of nocturnal leg cramps. Other centrally acting compounds include carisoprodol, chlorphensin, chlorzoxazone, diazepam, meprobamate and orphenadrine.
   Musculotropic spasmolytics act by a variety of mechanisms which include inhibition of phosphodiesterases, inhibition of sodium-dependent cAMP-mediated Ca²⁺ efflux, calcium channel antagonism and inhibition of adenosine reuptake carriers their effects probably due to a mixture of these mechanisms. Examples include papaverine (used for erectile dysfunction), ethaverine (a vasodilator used to treat circulatory disorders), moxaverine, caroverine and tiropramide.
Neurotropic- musculotropic spasmolytics have both musculotropic spasmolytic actions and parasympatholytic effects. Examples include dicyclomine (used to treat smooth muscle spasms in the intestines), oxybutinin (used to treat urinary frequency, urinary incontinence and neurogenic bladder instability) and flavoxate (used for urinary frequency, urinary incontinence and bladder spasms due to catheterization.
5) Other muscle relaxants include calcium  antagonists which act in vascular smooth muscle causing vasodilation. Examples include nifedipine, nitrendipine, verapamil and diltiazem.

Musculotropics: drugs affecting, attracted to or acting directly upon muscle tissue which are used as muscle relaxants. Examples of musculotropics include the papaverine-like spasmolytic agents such as papaverine, ethaverine and moxaverine.

Musk shrew: also known as the house musk shrew (Suncus murinus), has become an animal model for motion sickness and for investigations into the effects of emetics and antiemetics (rats cannot be used as they cannot vomit). The musk shrew is widely distributed in tropical and subtropical regions of the world and is commercially available from animal suppliers. This animal appears to respond to both emetic and anti-emetic drugs like humans and retches and vomits in response to certain kinds of intense motion.

Mustard gas: also known as ypertite, an oily liquid used in chemical warfare. It is a severe vesicant (it causes skin blistering), potent eye irritant and can cause respiratory failure.

Mutagenesis: relating to the generation of mutations in genes. Mutagens are substances causing mutations.

Mutual prodrug: a type of carrier-linked prodrug.

Mycophenolic acid (MPA): also known as mycophenolate, an immunosuppressant and antibiotic substance derived from Penicillium stoloniferum. It inhibits de novo synthesis of guanosine nucleotides by selective, uncompetitive and reversible inhibition of inosine monophosphate dehydrogenase . MPA inhibits the proliferation of T-cells, lymphocytes and the formation of antibodies from B-cells and may also inhibit recruitment of leukocytes into inflammatory sites.
It is used for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants and is usually administered in combination with cyclosporine and corticosteroids. It has also been used to treat severe refractory eczema.

Mycotoxins: toxins produced by fungi. Examples include ergot, botulinum and ochratoxins.

Mydriatic: a drug which causes mydriasis, dilation of the pupil of the eye.

Mydriatic alkaloids: also known as belladona alkaloids, alkaloids obtained from Atropa belladonna and other solanaceous plants. These alkaloids dilate the pupil of the eye and examples include hyoscyamine and atropine.

Myenteric plexus-longitudinal muscle preparation (MPLM): a muscle preparation commonly obtained from the guinea pig ileum which has one of the highest acetylcholine contents and richest cholinergic innervation of known mammalian tissues. Originally introduced by Paton and Zar in 1968, this tissue comprises ganglionic and neuromuscular synapses and has been used to investigate the role of both nicotinic and muscarinic agonists on mammalian muscle tissue.
Paton WD, Zar MA. The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol (1968) 194(1):13-33

Myoneural agents: compounds which facilitate or inhibit the contraction of striated muscle at the neuromuscular junction, ie compunds which affect cholinergic transmission. Myoneural compounds act in at least three ways; by receptor blockade such as that caused by curare, by affecting the activity of cholinesterase such as the potentiation caused by neostigmine and by affecting the syntheis and/or release of ACh such as that observed with botulinum toxin.