Nachmansohn's hypothesis: a hypothesis proposed by the American pharmacologist David Nachmansohn in the 1950s which suggested that acetylcholine plays an essential role not only at synapses and neuromuscular junctions but that it is is essential in the generation of action potentials in all nerve and muscle cell membranes. He suggested that a local current which moves slightly ahead of the propagation action potential released acetylcholine from its storage site in the cell membrane. The interaction between the released acetylcholine and specific receptors in the cell membrane cause increases in sodium permeability. Nachmansohn also suggested that the acetylcholine receptor is the calcium-binding subunit of the neuronal membrane.
Nachmansohn D. Chemical and Molecular Basis of Nerve Activity (1959) Academic Press, New York
Nadolol: a aryloxypropanolamine-type, lipid soluble β1-blocker and antihypertensive used clinically to treat hypertension and in the prophylaxis of migraine. See http://www.nadolol.com
Naive animal: an animal which has not been exposed to drugs, antigens or other stimuli and so one which is likely to express an enhanced reaction to such stimuli when the animal is first exposed to them. A primed animal is one which has been previously exposed to these stimuli.
Nakano mouse: a strain of mouse originally from Japan which shows a high incidence of cataract formation (it is a cataractous strain) and an animal used in the study of cataracts.
Iwata S, Kinoshita JH. Mechanism of development of hereditary cataract in mice. Invest Ophthalmol. (1971) Jul 10(7);504-12
Nalbuphine: a synthetic opioid analgesic used clinically to treat moderate to severe pain, in surgical premedication, in peri-operative analgesia and to treat myocardial infarction. It is an antagonist at the μ-opioid receptor and an agonist at κ-receptor. It is chemically related to naloxone, nalorphine, naltrexone and oxymorphone which are all phenanthrenes. The phenanthrene moiety is shown in blue in the diagram below.
Nalidixic acid: a quinolone antibacterial effective against both gram-positive and gram-negative bacterial and which is used clinically to treat urinary tract infections.
Naloxone: a synthetic opioid analgesic with a high affinity to μ-receptors and which is used clinically to induce the reversal of opioid-induced respiratory depression and overdoes of opioids. It acts by displacing the opioid agonists from its receptor binding site as ligand affinity for this receptor subtype is generally low. Naloxone is used postoperatively in animals to reverse respiratory depression induced by opioid anaesthetics.
Naltrexone: a long-acting, synthetic μ, κ and δ-opioid receptor antagonist used clinically as an adjunct to prevent relapse in detoxified former opioid addicted individuals who have remained opioid-free for more than 7 days. It is also used in veterinary pharmacology to treat behavioural problems in dogs such as continuous licking.
Naltriben: a competitive and selective antagonist of δ2-opioid receptors. Antagonism appears to be dependent on concentration and naltriben acts as an antagonist at δ receptors, as a noncompetitive antagonist at μ-receptors and as an agonist for κ2 receptors. It has been used as a pharmacological tool to investigate opioid receptors.
NANC: nonadrenergic, noncholinergic and a general term used to describe neurons which are neither adrenergic or cholinergic in nature. NANC neurons are often associated with the enteric nervous system (ENS) and include neurons releasing vasoactive intestinal peptide (VIP), substance P and somatostatin as neurotransmitters.
Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst. (2000) Jul 3;81(1-3); 87-96
NANCE: nonadrenergic, noncholinergic excitatory fibers.
NANCI: nonadrenergic, noncholinergic inhibitory fibers.
NANSAID: non-aspirin, non-steroidal anti-inflammatory drug.
α-Naphthylisothiocyanate (ANIT): a hepatotoxic compound which causes the separation of extracellular tight junctions which seal bile canaliculi leading to impaired bile secretion, retention of bile acids and consequent hepatotoxicity. It is used experimentally to cause hepatic injury and intrahepatic cholestasis.
4-(1-Naphthylvinyl)pyridine: also known as 4-NVP, an inhibitor of choline acetyltransferase which is known to deplete brain acetylcholine levels in treated animals. It has been used as a pharmacological tool to study ACH synthesis.
Napsylate: a sulphonate salt of naphthalene (2-naphthalenesulphonate). Napsylates are used in pharmaceutical formulations because they help mask the taste of the parent drug. Examples include dextropropoxyphene napsylate suspension which is used for pain relief.
Narcotics: a class of drugs derived from opium or opium-like compounds and which have potent analgesic effects. These drugs are associated with significant alteration of mood and behaviour and have the potential for the development of dependence and tolerance following repeated administration.
Narcotic antagonists: compounds which inhibit the effects of narcotics on the central nervous system. Examples include methadone and naloxone which are used clinically to treat narcotic dependence. Methadone is, in fact, a opioid agonist which is usually substituted for opioids such as heroin so preventing the onset of withdrawal symptoms in addicts.
Narrow spectrum: a term used to describe a drug which has small range of efficacy and is particularly used for antibiotics. Narrow-spectrum antibiotics include phenoxymethicillin, phenethicillin and benzylpenicillin which are used clinically against throat infections, otis media, streptococcal endocarditis, meningiococcal meningitis and pneumonia.
Nateglinide: an oral antidiabetic drug used to treat type 2 diabetes mellitus particularly in combination with metformin when metformin on its own is not effective. Nateglinide stimulates insulin release.
Natriuretic: a substance which causes the excretion of sodium ions in the urine. Examples include the endogenous natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide), calcium antagonists such as verapamil and gallopamil which show a weak effect and thiazide diuretics such as hydrochlorothiazide.
NBM: nucleus basalis magnocellularis
NCE: new chemical entity
NDA: new drug application.
NECA: 5'-N-ethylcarboxamidoadenosine, a non-selective A1/A2 adenosine receptor agonist.
Negative agonist: a type of agonist.
Negative efficacy: a type of efficacy observed for a ligand at a receptor site but which is actually inverse agonist activity. An example is benzodiazepine receptor ligands which produce effects opposite to those of benzodiazepines, ie they produce convulsions and anxiety. They have negative efficacy at benzodiazepine receptor sites.
NEL: also referred to as the NOAEL (no-observed-adverse-effect-level ), a concentration in a series of doses tested which is the highest at which no effect is observed, ie a dose which is safe in the species tested.
Nematocides: also known as antinematodal agents, compounds which kill nematodes (intestinal roundworms, threadworms, lungworms, whipworms, hookworms, pinworms, ascarids, and filarids). Nematodes can be free living or parasitic and cause a variety of diseases in humans and animals including trichinosis (a disease causes by consuming Trichinella spiralis (commonly called the trichina worm) which causes gastrointestinal upset, diarrhoea, fatigue and fever.
Nematocides are classified as narrow spectrum, eg phenothiazines (thiabendazole, albendazole), piperazine, toluene and thenium closylate and broad spectrum, eg benzimidazoles, organophosphates (dichlorvos, antibiotics (ivermectin) and nicotine-like compounds (levamisole, butamisole). For example, thiabendazole is used in ruminants and horses and acts by inhibiting fumarate reductase and inhibits the formation of succinate from fumarate. This in turn leads to a decrease in ATP formation.
Neonatal: the period from birth to 1 month of age.
Neostigmine: also known as synstigmin, prostigmine and proserine, a quarternary ammonium compound (3-[[(dimethylamino)carbonyl]oxy]-N,N,N-trimethylbenzenaminium) and medium-duration of action reversible anticholinesterase. It enhances cholinergic transmission and is used clinically to treat myasthenia gravis (a muscle weakening and fatiguing disorder caused by the destruction of acetylcholine receptors by autoantibodies), to reverse the effects on non-depolarizing (competitive) muscle relaxants used in surgery and sometimes as a stimulant laxative as it enhances parasympathetic activity in the gut and increases intestinal motility. Neostigmine acts at the neuromuscular junction to enhance cholinergic transmission and side effects tend to be peripheral rather than central and include bradycardia, hypotension, bronchoconstriction, sweating, gastrointestinal hypermotility and decreased intraocular pressure (it is effective in glaucoma).
Neosurugatoxin (NSTX): a neurotoxin and selective antagonist of ganglionic nicotinic acetylcholine receptors. It can be isolated form the Japanese ivory mollusc (Babylonia japonica) and has been used as a pharmacological tool to study nicotinic receptors.
Hayashi E et al. Neosurugatoxin, a specific antagonist of nicotinic acetylcholine receptors. Journal of Neurochemistry. (1984) 42(5);1471-4
NEP: neutral endopeptidase
NEP inhibitor: neutral endopeptidase inhibitor
Nephrotrophic: also known as renotrophic, affecting the kidneys.
Nerve gases: a group of organophosphorus compounds used in chemical warfare. They are potent anticholinesterases and exposure to them leads to muscle paralysis particularly the intercostal muscles and diaphragm leading to pulmonary failure.. The principal members of this group are sarin, soman, and tabun. They are usually liquids at room temperature but can easily be volatilised and, as they are inhaled, have particularly potent effects on the lungs.
http://en.wikipedia.org/wiki/Nerve_gas
Nervous pointer dog: a genetic animal model of anxiety.
NETA: (α-NETA (2-(α-naphthoyl)ethyltrimethylammonium iodide), a potent, selective, stable and fluorescent inhibitor of choline acetyltransferase. β-NETA ((2-(β-naphthoyl)ethyltrimethylammonium iodide) a selective inhibitor of choline acetyltransferase and has been used as a pharmacological tool in the investigation of acetylcholine synthesis.
Neuraminidases: a group of glycoside hydrolase enzymes expressed on the surface of viruses where they act to facilitate the release of viruses from cells and their transmission to neighbouring cells. Several isozymes are known.
Neuraminidase inhibitors: compounds which inhibit the actions of neuraminidase and which are used clinically in the treatment of viral infections. Examples include zanamivir and oseltamivir which are used clinically to treat influenza A and B virus infections.
Neuregulins: a family of proteins which are important in the developing nervous system particularly in formation and stabilization of neuromuscular junctions. There are 2 isoforms, neuregulin 1 and neuregulin 2. Neuregulins have acetylcholine receptor inducing activity (ARIA) and can increase the expression of ACh receptors at the neuromuscular junction. Neuregulin-1 is thought to be a trigger for the production of myelin during neuronal development and to play a role in schizophrenia.
Esper RM et al. Neuregulins: versatile growth and differentiation factors in nervous system development and human disease. Brain Res Brain Res Rev (2006) 51(2);161-75
Neuroactive steroids: also known as neurosteroids, a group of steroidal compounds which modulate neuron excitability and transmission. They are synthesized in both the central and peripheral nervous systems (particularly in Purkinje cells) from cholesterol or steroidal precursors. Neurosteroids include pregnenolone, allodeoxycorticosterone and dehydroepiandrosterone. These compounds function as allosteric modulators of neurotransmitter receptors such as NMDA, GABAA and sigma receptors. Progesterone and allodeoxycorticosterone have anticonvulsant actions while oestradiol and cortisol have proconvulsant action and may be of use in the development of drugs which modulate the actions of neurosteroids in treating these disorders. Synthetic neurosteroids such as alphaxolone, ganaxolone and Co 21068 have show protective effect in animals models of various seizures.
Belelli D et al. Neuroactive steroids and inhibitory neurotransmission: mechanisms of action and physiological relevance. Neuroscience (2006) 138(3);821-9
Neurobiological tool: a term used to describe compounds that are used as pharmacological tools in neurobiology to selectively cause lesions in parts of the brain especially in specific areas which are innervated by neurones utilizing a known transmitter. These compounds are used to disrupt or destroy specific neurotransmitter actions in the development of animal models of neurodegenerative disease. Examples include 6-hydroxydopamine, kainic acid, tetanus toxin and tetrodotoxin.
Neurocrine: also referred to as neurosecretory, refers to transport of a neurohormone from the cell body of a neuron along its axon and then in the blood to its target cells.
Neuroendocrine: relating to the interactions between the nervous and endocrine systems. This term is used to describe certain cells that release hormones into the blood in response to stimulation of the central or peripheral nervous systems.
Neuroleptanalgesia: a state of sedated analgesia, quiescence, altered awareness and analgesia produced by the co-administration of an opioid analgesic such as fentanyl and a neuroleptic agent such as the tranquilizer droperidol. Neuroleptanalgesia is used, for example, when carrying out an endoscopic examination of the gut.
Neuroleptic: also known as antipsychotics and drugs used to treat psychoses such as schizophrenia. Examples of neuroleptics include chlorpromazine, thioridazine, haloperidol, flupenthixol, sulpiride, clozapine, risperidone, sertindole and seroquel.
Neuroma model: an animal model of neuropathic pain.
Neuromuscular blockers (NMB): compounds which block neurotransmission across the neuromuscular junction at nicotinic receptors sites thereby decreasing skeletal muscle tone. They are used in surgery usually as premedication. They are classified into two main types, depolarizing and non-depolarizing.
- Non-depolarizing neuromuscular blockers compete with ACh for nicotinic receptor binding sites on the muscle cells. Blockade is competitive so muscle paralysis occurs gradually. Examples include tubocurarine, rocuronium, cisatracurium, gallamine, atracurium, vecuronium and mivacurium.
- Depolarizing neuromuscular blockers produce a long-lasting depolarization of the nicotinic receptor by mimicking the effects of ACh but which are not rapidly hydrolysed by acetylcholinesterase. Examples include suxamethonium and decamethonium.
Neuronal uptake: the uptake of monoamine neurotransmitter by a neuron after it has been released thereby decreasing the numbers occupied by the neurotransmitter and thus decreasing the response to the transmitter. There are two main uptake mechanisms, uptake 1 and uptake 2 and they apply to various neurotransmitters particularly catecholamines but often refer to noradrenergic neurons.
Neuronal uptake is known as uptake 1 and involves the reuptake of neurotransmitter into the presynaptic neuron and comprises the main route of inactivation of the sympathetic neurotransmitter norepinephrine for example. Uptake 1 relies on a high-affinity, Na+- and Cl−-dependent membrane noradrenaline transporter.
Uptake by an extraneuronal monoamine transporter into adjacent neurons such as glial cells known as uptake 2.
Axelrod J, Kopin IJ. The uptake, storage, release and metabolism of noradrenaline in sympathetic nerves. Prog Brain Res (1969) 31; 21-32
Amara S G, Kuhar M J. Neurotransmitter transporters: recent progress. Annu Rev Neurosci (1993) 16;73-93
Neuronal uptake 1 inhibitors: compounds which inhibit the reuptake of released neurotransmitter into the presynaptic neuron thereby enhancing the effects of the neurotransmitter at the synaptic cleft. Examples include desipramine, desmethylimipramine, nisoxetine, cocaine and GBR12909 which are inhibitors of noradrenaline reuptake.
Neuronal uptake 2 inhibitors: compounds which inhibit the uptake of released neurotransmitter into extraneuronal cells. Examples include 3-O-methoxyisoprenaline, normetanephrine and disprocynium 24.
Neurotensin: 13-amino acid brain-gut peptide found in the brain, spinal cord and a gastrointestinal tract. It delays gastric emptying and has various neurological functions.
St-Gelais F et al. The role of neurotensin in central nervous system pathophysiology: what is the evidence? J Psychiatry Neurosci (2006) 31(4);229-45
Neuropeptides: any (generally) short-chain peptide found in neural tissue and often coexistent with neurotransmitters such as noradrenaline, GABA and dopamine. Many have neurotransmitter functions Examples of neuropeptides include endorphins, enkephalins, substance P, neurokinin and calcitonin gene-related peptide. This family currently comprises a family of over 100 peptides.
Neuropeptide Y (NPY): also known as neuropeptide tyrosine because of its five tyrosine (which is assigned the amino acid code Y) residues, a 36 amino acid peptide discovered in 1982 and the most abundant known peptide in mammalian brain. It is also present in the peripheral nervous system and adrenal medullary cells. NPY has been shown to exhibit a wide range of effects mediated by a growing number of NPY receptors in both the CNS and peripheral nervous system and include the abolition of anxiety (anxiolysis), sedation, vasoconstriction and stimulation of food intake.
A major role of NPY is the control of systemic blood pressure and also its effects on feeding, anxiety and memory. It may play an important role in mediating analgesia and hyperalgesia by peripheral and central mechanisms and may play a role in a broader range or disorders including anorexia, epilepsy, depression, hypertension and heart failure.
Munglani R, Hudspith MJ, Hunt SP. The therapeutic potential of neuropeptide Y. Analgesic, anxiolytic and antihypertensive (1996) Drugs, 52: 371-389
Neuropeptide Y receptors: a family of pertussis toxin-sensitive G protein-coupled receptors belonging to the 7-transmembrane receptor family for which neuropeptide Y is an endogenous ligand. This family currently comprises five receptor subtypes, Y1 to Y5. They mediate the actions of neuropeptide Y and so mediate food intake and gastrointestinal function, ie they mediate the anabolic effector signalling and energy intake-stimulating effects of NYP.
See www.iuphar-db.org/GPCR/IntroductionDisplayForward? chapterID=1292
Martin C, Michel et al. International Union of Pharmacology Recommendations for the Nomenclature of Neuropeptide Y, Peptide YY, and Pancreatic Polypeptide Receptors . Pharmacological Reviews. (1998) 50(1); 143-150
Neuroplegic: relating to paralysis resulting from disease of the nervous system or a drug acting on it.
Neurosteroid: also known as neuroactive steroids, steroids found in the nervous system including compounds structurally related to cortisone, progesterone and gonadal hormones. They play important roles in depression and anxiety. Neurosteroids are also important in neuronal development and have neuroprotective effects. The term neurosteroid was introduced by Baulieu in 1981 in reference to dehydroepiandrosterone sulphate (DHEAS) which was found in high concentrations in the brain a long time after gonadectomy and adrenalectomy had been carried out. Neurosteroids are synthesized in the central and peripheral nervous systems and are particularly prevalent in myelinating glial cells. They are synthesised from cholesterol or steroidal precursors from peripheral sources.
Neurotensin: a 13 amino acid brain/gut peptide which exerts neuromodulatory functions in the central nervous system and endocrine/paracrine actions in the periphery. It has been implicated in the biology of schizophrenia as it is thought to modulate, dopaminergic and other neurotransmitter systems involved in this psychosis.
Caceda R et al. Neurotensin: role in psychiatric and neurological diseases. Peptides (2006) 27(10);2385-2404
Neurotensin agonists: compounds which stimulate or promote the actions of neurotensin and which are of potential use in the treatment of schizophrenia. This is largely due to their ability to inhibit dopamine 2 (D2) receptor transmission. Examples of neurotensin agonists include PD149163 and NT69L.
Boules M et al. Neurotensin agonists : potential in the treatment of schizophrenia. CNS Drugs (2007):21(1);13-23
Neurotensin receptors: a family of three G protein-coupled receptors, NTS1, NTS2 and NTS3 which mediate the effects of neurotensin.
Neurotoxins: any compound which is toxic to nerves and caused damage or disruption to their function. They are often found in the venoms of poisonous animals such as snakes and scorpions. They tend to have several distinct mechanisms of action, for example, sodium channel blockers like tetrodotoxin and batrachotoxin, whereas maurotoxin, agitoxin and charybdotoxin block potassium channels and calcicludine and taicatoxin act on calcium channels. Apart from their uses in animal hunting, they are generally used as pharmacological tools to study ion channel function and consequent inhibition of nerve impulse propagation. Simpler compounds and elements can be neurotoxins too such as mercury and cyanide.
Some neurotoxins have clinical application. Botulinus toxin, for example, is used to treat various ophthalmic diseases such as dystonic movement disorders, strabismus and nystagmus.
Neurotransmitter: a compound usually synthesised by a nerve cell and which is used to communicate a signal to another nerve cell by release across an interneuronal space and stimulation of a specific receptor on the receiving cell. See http://en.wikipedia.org/wiki/Neurotransmitter.
Neurotrophins: also known as neurotrophic factors, substances which support the growth and survival of neurones and which include nerve growth factor, brain-derived growth factor, neurotrophin 3 and neurotrophin 4. These substances are usually present in blood and signal particular cells to survive, or differentiate, or grow largely by inhibiting cells to initiate apoptosis. Neurotrophins are thought to be of use in the treatment of neurological damage associated with Alzheimer's disease, stroke and cancer.
Neurotrophin receptors: cell surface receptors for which the endogenous ligands are neurotrophins. There are two main types of neurotrophin receptors which determine the survival of the nerve cell. The TRK receptors typically communicate a positive signal to the cell, promoting its survival or growth. The p75 neurotrophin receptor typically promotes cell death.
Hennigan A et al. Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans (2007) 35 (2): 424-7
Neutral antagonism: a form of antagonism.
Neutral endopeptidase (NEP): also known as neprilysin and endopeptidase 24.11, a widely distributed ectoenzyme (EC 3.4.24.11), cleaves and inactivates a variety of biologically active peptides including tachykinin,g;ucagon substance P . It is also implicated in the metabolism of peptides involved in blood pressure and sodium homeostasis control including angiotensins, atrial natriuretic factor (ANF), bradykinin and endothelin.
Neutral endopeptidase inhibitor (NEPI): compounds which inhibit the activity of neutral endopeptidase. Examples include the specific and potent SCH 39370, thiorphan (an active metabolite of racecadotril), candoxatril (UK-79,300, a prodrug hydrolyzed in the liver to candoxatrilat) and omapatrilat which also inhibits angiotensin converting enzyme. They may have use in the treatment of heart failure and hypertension.
New chemical entity (NCE): also known as a new molecular entity (NME), a compound of potential use as a drug in therapy.
Nicardipine: a dihydropyridine-type calcium antagonist used in the treatment of hypertension and angina. It is structurally related to other calcium channel blockers such as amlodipine, felodipine, israpidine and nislodipine. Calcium channel blockers work by blocking L-type voltage gated calcium channels in the heart and vascular tissue preventing calcium levels from increasing as much as normal in these cells when stimulated. Consequently, less contraction is possible. The dihydropyridine moiety is shown in blue below.
Nicotine: one of a family of Nicotiana alkaloids which is present in all plants of this genus. It is biosynthesized in the roots and transported to other parts such as the leaf where it is present at levels of between 0.05 and 10%. The dried leaves of these plants are shredded and turned in to tobacco products for smoking. Nicotine is the most widely used addictive alkaloid and is consumed orally or by inhalation from products made from the leaves of tobacco plants.
Nicotinic acid: also known as niacin and vitamin B3, a water-soluble vitamin present whose derivatives include NADH, NAD, NAD+, and NADP and which are important in cell metabolism. Some other derivatives also have antihyperlipoproteinaemic effects and include nicomol, oxinaicic acid and niceritrol.
Nicotinic cholinoceptors: pentameric, ionotropic receptors for acetylcholine which form ligand gated ion channels and which are distributed in neuromuscular junctions and in ganglionic synapses. There are several types of nicotinic receptors:
- muscle (of which there is 1 subtype, IV)- present in the skeletal neuromuscular junction and which modulate neuromuscular transmission. Agonists of this receptor subtype include acetylcholine, carbamylcholine, suxamethonium and decamethonium. Antagonists include tubocurarine, pancuronium, atracurium and α-bungarotoxin.
- neuronal (of which there are 3 subtypes, I, II and III) - present in autonomic ganglia, sensory nerve terminals and in many areas of the CNS. They modulate ganglionic transmission and presynaptic facilitation in the CNS. Agonists of this receptor subtype include acetylcholine, carbamycholine, nicotine, lobeline, epibatidine and DMPP. Agonists include mecamylamine, trimetaphan and hexamethonium
Lukas RJ et al. International Union of Pharmacology. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacological Reviews. (1999) 51; 397-401
Nictitating membrane: a third eyelid present in some animals such as cats and chickens which can be drawn over the eye for protection. It is made of smooth muscle.
NIDDM: non-insulin dependent diabetes mellitus.
Nifedipine: a calcium channel blocker used clinically to treat hypertension and Raynaud's phenomenon and in the prophylaxis of angina. It is a vasodilator.
Nigericin: a K+/H+ ionophore and an antibiotic derived from Streptomyces hygroscopicus.
Nigrostriatal pathway: a group of dopaminergic neurones originating (ie with their cell bodies) in the substantia nigra and their axons terminating in the corpus striatum. About 75% of all central dopaminergic neurones occur in this pathway and it is essential in transmitting signals for fine motor movements and damage to the neurones in the nigrostriatal pathway leads to parkinsonsism.
(S)-(+) Niguldipine: a dihydropyridine derivative and selective antagonist of a1A-adrenoceptors (with high affinity for L-type calcium channels). It is used as a pharmacological tool to investigate these receptors and ion channels.
Nikethamide: a respiratory stimulant no longer used clinically due to toxicity but which was once used to promote breathing in cases of barbiturate overdose. It has also been used as a stimulant in sport dosing. Nikethamide acts by both stimulating the medullary centres and by stimulating the carotid bodies. It also sensitizes the respiratory centre to CO2.
NIMA kinase: a protein-Ser/Thr kinase which is biochemically distinct from other protein kinases. Its phosphotransferase activity is regulated by Ser/Thr phosphorylation
Nipecotic acid: a competitive inhibitor of GABA transporters which acts as a GABA uptake inhibitor. It is used as a pharmacological tool to investigate GABA transport.
Krogsgaard-Larsen P et al. GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects. Curr Pharm Des (2000) 6(12):1193-209
Nitrazepam: a benzodiazepine derivative and psychotropic agent used clinically for the short-term treatment of insomnia (ie, it is used as a hypnotic). Like all benzodiazepines, it acts by modulating GABA-mediated neurotransmission.
Nitrergic: relating to nitric oxide. Nitrergic neurones release nitric oxide as their transmitter.
Nitric oxide (NO): originally known as EDRF (endothelium-derived relaxing factor), a free radical and potent signalling molecule with marked effects on vascular tissue, cellular immunity, angiogenesis, neurotransmission and platelet aggregation. It is produced in vascular endothelial cells and is a potent vascular smooth muscle relaxant. In fact, nitric oxide is the subject of a journal dedicated to it; Nitric Oxide, Biology and Chemistry from the Nitric Oxide Society.
The release of NO from organic nitrates such as nitroglycerin explains their vasodilatory actions in angina.
Nitric oxide donor: a compound which release NO to surrounding tissue and so a compound of use in the treatment of vascular disorders. Examples include S-nitrosoglutathione, streptozotocin and E 175.
Millar MR et al. Recent developments in nitric oxide donor drugs. Br J Pharmacol (2007) Apr 2
Nitric oxide synthase (NOS): a family of three heme isozymes which produce nitric oxide by the oxygen-dependent oxidation of a terminal nitrogen on the guanidine of L-Arginine. They are neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) and NOS was first identified by Furchgott in 1980
Nitrofurans: a class of synthetic, broad-spectrum bacteriostatic compound which include nitrofurazone and nitrofurantoin (which is used clinically to treat urinary-tract infections in humans cats and dogs and is used topically as an antibacterial ointment in many species of animals). Nitrofurans are reduced by bacteria to form a reactive intermediate which inhibits the enzymes involved in carbohydrate synthesis and also inhibit mRNA translation. The nitrofuran moiety is shown in blue below.
Nitrogen mustards: irritants and vesicants (they cause blistering) related to sulphur mustards. They are used clinically to treat multiple myeloma, advanced ovarian carcinoma, advanced breast cancer, neuroblastoma and lymphocytic leukaemia. They are potent alkylating agents which inhibit DNA and cellular replication. Examples include cyclophosphamide, ifosfamide, estramustine and melphalan. Nitrogen mustards were used in the First World War as poisonous gases.
Nitroimidazole antifungals: See metronidaole.
3-Nitropropionic acid: an inhibitor of succinate dehydrogenase and a dietary neurotoxin.
Nitroprusside: an NO donor.
4-Nitroquinoline 1-oxide: a chemical carcinogen.
S-Nitroso-acetylpenicillamine: an NO donor.
N-nitrosobis(2-oxopropyl)amine (BOP): a chemical carcinogen used to induce tumours particularly in the pancreas in animal models of carcinogenesis particularly in Syrian hamsters. Typically, a dose of BOP of 10, 20 or 40 mg /kg body given subcutaneously every week and tumours develop by about week 3 of treatment. BOP has also been use as an initiator of carcinogenesis prior to treatment with other carcinogens.
Nitrosoureas: alkylating agents used to treat cancers such as Hodgkin's disease and some solid tumours. Examples include lomustine and carmustine. They are lipid soluble and so can enter the brain. Streptozotocin is a naturally occurring nitrosourea obtained from Streptomyces acromogenes. The nitrosourea moiety is shown in blue below.
Nitroxidergic: relating to nitric oxide.
NMB: neuromuscular blocker.
NMDA: N-methyl-D-aspartate
NMJ: neuromuscular junction.
NMS (N-methylscopolamine): a muscarinic cholinoceptor antagonist used as a pharmacological tool to investigate the function of muscarinic receptors.
NNRTI: non-nucleoside reverse transcriptase inhibitors (see HIV reverse transcriptase).
NO: nitric oxide
NO donor: a compound which can donate nitric oxide to a reaction either by spontaneous release or by enzymatic release. Examples of NO donors include nitroglycerin which donates NO to cause vasodilation and PF9404C which acts as a vasodilator and a β-blocker. NO donors are largely used as pharmacological tools to investigate the physiological role of NO although some are used clinically or are in clinical trials to treat vascular diseases, pulmonary hypertension and impotence. A list of NO donor compounds can be found at:
http://home.ncifcrf.gov/lcc/nitricoxide/CompoundSearch/CompoundSearchR esult.asp
Ignarro LJ et al. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide (2002) Circulation Research, 90:21
http://circres.ahajournals.org/cgi/content/full/90/1/21
No-adverse-effect level (NEL): a parameter used in estimating the hazard presented by environmental chemicals. It is being slowly replaced by more sensitive toxicological parameters as it incorrectly assumes that there is a level up to which each chemical can be tolerated by humans before exhibiting toxic effects.
Nociceptin: a neuropeptide derived from prepronociceptin and which plays important roles in the regulation of pain transmission (it blocks pain transmission) and learning and memory in the central nervous system. Nociceptin is an endogenous ligand for the orphan opioid-like receptor and is being used as a pharmacological tool in the development of drugs to treat pain.
Nociceptin receptor: a type of opioid receptor.
Nociception: the perception of noxious stimuli including the perception of pain.
Nociceptors: receptors selectively sensitive to noxious stimuli or stimuli which become noxious if exposure to them is prolonged. They are sensitive to the effects of chemical and/or physical injury. They are present in the central and peripheral nervous systems and their activation is manifested in what is most commonly referred to as pain.
Nocifensive: relating to the type of defensive behaviour observed when an animal is subjected to a noxious stimulus such as the injection of formalin solution into a paw (the formalin test). The immediate response is withdrawal of the paw.
Nocistatin: a neuropeptide which blocks nociceptin-induced allodynia and hyperalgesia.
Nocodazole: also known as oncodazole, a promoter of tubulin depolymerization and inhibitor of mitosis ([5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl]-carbamic acid methyl ester). It has anticancer actions as it inhibits cell replication.
NOD mouse: an animal model for insulin-dependent diabetes mellitus. It is also used to study the pathogenesis of autoimmune thyroiditis.
Nomifensine: an atypical antidepressant drug which does not have a tricyclic structure (unlike many other antidepressants) and with similar noradrenaline blocking effects (it inhibits noradrenaline reuptake) to tricyclic antidepressants. Nomifensine also acts as a dopamine uptake inhibitor and to a lesser extent inhibits 5-HT reuptake. It was used as a non-opioid analgesic but has been withdrawn from clinical use.
Non-adrenergic/noncholinergic (NANC): see NANC.
Non-aspirin non-steroidal anti-inflammatory drug (NANSAID): anti-inflammatory compounds which are neither aspirin or have a steroid structure. Examples include naproxen.
Non-classical bioisosteres: chemical groups or atoms which do not follow the strict steric and electronic definitions a of classical isostere and which do not have the same number of atoms as the substituent moiety which they replace. They usually have similar biological activity as the parent molecule by mimicking the spatial arrangement and electronic properties of the parent.
Non-classical isostere: the same as bioisostere, ie a compound resulting from the exchange of an atom or of a group of atoms with a similar group in order to create a novel compound with similar biological properties to the parent compound.
Non-competitive antagonism: a type of antagonism.
Non-depolarizing drug: a type of neuromuscular blocker.
Non-desensitizing antagonism: a type of antagonism.
Non-equilibrium antagonist: a type of antagonist.
Non-genotoxic: describes substances which are toxic to cells but not at the DNA or RNA level where genotoxic compounds act.
Nonproprietary name: the official, approved or generic name of a drug and is the name by which most drugs are known. Examples include aspirin, valium, fluoxetine and paracetamol. International non-proprietary names are determined by The World Health Organisation. See www.who.int/medicines/services/inn/en/.
Nonspecific antagonism: a form of antagonism.
Nonsteroidal anti-inflammatory drug (NSAID): any compound with anti-inflammatory actions which does not have a steroid structure. The first one used clinically was probably acetylsalicylic acid (aspirin) which was used originally in 1899 and is still in common use. NSAIDS inhibit the production of prostaglandins and other eicosanoids by inhibiting cyclooxygenase. Examples of NSAIDS include salicylates (aspirin, diflunisal, ethenzamide, salicylamide), para-aminophenol derivatives (paracetamol, phenidine), anthranilates (etofenamate, flufenamic acid, meclofenamic acid, mefenamic acid, niflumic acid), arylacetic acids (acemetacin, bufexamac, diclofenac, indomethacin, lonazolac, sulindac, tolmetin, nabumetone), arylpropionic acids (flubiprofen, ibuprofen, ketoprofen, naproxen), pyrazolinone derivatives (metamizol, propyphenazone), pyrazolidine-3,5-diones (kebozone, mofebutazone and oxyphenbutazone) and oxicams (isoxicam, lornoxicam, piroxicam, tenoxican).
Nootropic: also known as smart drugs, compounds which act as cognitive enhancers (they increase cognition, lucidity, memory, mood, oxygen and glucose utilization and/or the flow of blood in the brain) with little or no side effects or toxicity. Nootropic comes from the Greek words noos meaning the mind and tropos meaning growth. Examples of nootropics include compounds which replenish and increase neurotransmitter levels such as cholinergics (DMAE (dimethylaminoethanol), huperazine A, piracetam), dopaminergics (tyrosine, yohimbine), serotoninergics and other compounds.
Nor: a chemical prefix used to show that ring contraction or loss of a methyl group from the carbon skeleton has occurred. Nor is an abbreviation of the German nitrogen ohne radikal. Examples include noradrenaline which is a demethylated form of adrenaline, norcodeine which is demethylated codeine and norpseudoephedrine which is demethylated pseudoephedrine. Some examples are shown below.
Noradrenaline: also known as norepinephrine, arterenol and levarterenol, a hormone and catecholamine neurotransmitter in the central and peripheral sympathetic nervous systems. Noradrenaline causes contraction of blood vessels (with the exception of coronary blood vessels) and so causes an increases in blood pressure. It relaxes smooth muscle but stimulates cardiac muscle. Noradrenaline is deactivated by O-methylation by the enzyme catechol O-methyltransferase and by a monoamine oxidase which removes the NH2 group to produce 3-methoxy-4-hydroxymandelic acid. It is also converted to adrenaline by phenylethanolamine N-methyl transferase.
Noradrenergic neurone-blocking agent: compounds which inhibit the release of noradrenaline from noradrenergic neurones. They act by a variety of mechanisms and include guanethidine (which inhibits the release of noradrenaline from noradrenergic neurones) and bretylium (which causes initial catecholamine release and then longer inhibition of noradrenaline release). Guanethidine has been use to treat hypertension and bretylium is sometimes used to treat ventricular dysrhythmias.
Norethisterone: also known as norethindrone chiefly in the US, a synthetic derivative of testosterone which has progesterone-like activity and some androgenic activity (ie stimulates the development of male sex characteristics). It is used clinically as an oral contraceptive, to treat endometriosis, dysfunctional uterine bleeding, dysmenorrhoea, premenstrual syndrome, postponement of menstruation, in hormone replacement therapy and to treat breast cancer. Norethisterone induces secretory changes in the oestrogen-primed endometrium, it induces the formation of thick, viscous cervical mucous, it inhibits the release of leutenizing hormone and inhibits ovulation.
Nostrum: from nostrum remedium meaning 'our remedy' in Latin and referring to patent medicines, ie medicines whose doubtful efficacy and whose ingredients are usually kept a secret.
Nortriptyline: a tricyclic thioxanthine antidepressant used clinically to treat depressive illness, nocturnal illness in children and neuropathic pain. It is a metabolite of amitryptyline and, like most tricyclic antidepressants, it block the uptake of amines by nerve terminals by competing with the binding site of the transporter protein. They also block uptake of 5-HT and adrenaline into synaptosomes.
Noxiustoxin (NTX): a 39 amino acid peptidyl K+-channel blocker isolated from the venom of the Mexican scorpion (Centruroides noxius). It has been used as a pharmacological tool to investigate these ion channels.
NPY: neuropeptide Y
NSAID: also known as non-steroidal anti-inflammatory agents (NSAIA), nonsteroidal anti-inflammatory drugs.
NSB: non-specific binding, in a ligand-receptor binding assay some ligand binds to its target receptor (specific binding) and other ligand binds to tissues, membranes and proteins in the adjacent environment. This form of binding is generally dependent on charge and hydrophobicity of the ligand.
NSY (Nagoya-Shibata-Yasuda) mouse: an inbred strain of mouse showing spontaneous development of diabetes mellitus. It was developed by selective breeding for the glucose intolerance trait from outbred Jcl:ICR mice. These mice develop diabetes mellitus in an age-dependent manner with a cumulative incidence of diabetes of 98% in males and 31% in females at age about 1 year.
NTS: nucleus tractus solitarius
NTX: noxiustoxin
Nuclear receptors: a family of ligand-activated transcription factors which bind to specific sequences of DNA upstream of target genes to control their transcription. Nuclear receptors are important in embryonic development, cell differentiation and homeostasis. They also play an essential role in the activity of hormones, autacoids and drugs including steroids such as oestrogens, progesterone, androgens, glucocorticoids, mineralocorticoids, peroxisome proliferators and vitamin D, retinoic acids, thyroid hormones, fatty acids, leukotrienes and prostaglandins.
Nucleus basalis magnocellularis (NBM): a basal nucleus in the basal forebrain complex which plays an important role in memory. It is the origin of cholinergic neurones which project into the cerebral cortex. Lesions of the NBM in rats cause impaired learning and memory and this is an important animal model of Alzheimer's disease. The NBM can be selectively and stereotactically destroyed by ibotenic acid.
Nucleus tractus solitarius (NTS): a brainstem nucleus on each side of the upper medulla which lies lateral to the dorsal nucleus of the vagus and to which it has many connecting neurones. The inferior area of this nucleus receives fibres from the vagus nerve and the NTS is important in blood pressure control, cough, gag and sneezing reflexes, vomiting and inspiration.
Nucleoside antibiotics: synthetic or naturally occurring purine or pyrimidine nucleosides with antibiotic, antitumour, antimitotic and immunosuppressant activity. Nucleoside antibiotics comprise a heterocyclic base aglycone and a carbohydrate or a carbocyclic ring linked via a C-N bond (N-Nucleosides) or a C-C bond (C-nucleoside) They prevent microorganism growth by acting as antimetabolites of natural substrates and are active against fungi, viruses and certain cancer cells. Examples of N-nucleoside antibiotics include 5-azacytidine, bredinin, coformycin, cordycepin, crotonoside, nebularine, toyocamcin and polyoxins. Examples of C-nucleoside antibiotics include formycin and showdomycin. Carbocyclic nucleoside antibiotics include aristeromycin and neplanocin A.
Nucleoside transporters: cell membrane transporter mechanisms which uptake nucleosides from the extracellular space and which are essential for nucleotide synthesis. Some anticancer drugs enter cells via this transporter system and depend on it to exert their anticancer activity. Examples of such drugs include gemcitabine.
King AE et al. Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci (2006) 27(8);416-25
Nude mouse: an immunodefficient mouse originally developed in the late 1970s which is hairless, has an albino background and does not have a thymus. It is therefore unable to mount a normal cellular immune response such as in xenograft rejection as it lacks T helper and cytotoxic cells. It also has markedly reduced or absent IgG levels. Nude mice are highly susceptible to opportunistic infections and must be reared in pathogen-free conditions such as in an isolator. Female nude mice cannot rear their litters to weaning.
Nude mice are often used in determining the effects of anticancer drugs in vivo by implanting tumours into them particularly under their skin. The effects of a test drug against the tumour can be investigated without interference from the animals immune system which would normally reject the tumour.
Nutrigenomics: also known as nutritional genomics, the study of the relationship between nutrients and gene expression. based on the assumption that certain nutrients can alter gene expression or epigenetic phenomena to induce a normally healthy phenotype to develop chronic diseases.
García-Cañas V et al. Advances in Nutrigenomics research: Novel and future analytical approaches to investigate the biological activity of natural compounds and food functions. J Pharm Biomed Anal (2009) May 3
Number of receptors (N): also known as receptor density.
Nyctohemeral: relating to the nycthemeron which is the full 24-hour cycle of night and day.
Nystatin: a polyene antifungal used clinically against Candida albicans infections of the mouth and mucous membranes including the vulva, vagina, skin and perianal regions. Nystatin binds to ergosterol (a major component of fungal cell walls) and acts as an ionophore causing leakage of cations and cell death.
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