Cathepsin A, also known as carboxypeptidase C, is a serine carboxypeptidase (EC 3.4.16.5) and a multifunctional enzyme which possesses deaminidase and esterase activities at neutral pH and carboxypeptidase activity at acidic pH. It is considered to be a protective protein and its association with β-galactosidase and neuraminidase is essential for β-galactosidase stability and neuraminidase activation in lysosomes. Inherited cathepsin A deficiency causes the galactosialidosis which is a lysosomal storage disorder.
Cathepsin C, also known as DPPI (dipeptidyl peptidase I), is a cysteine protease (EC 3.4.14.1) which sequentially removes dipeptides from the free N-termini of proteins and peptides and functions in lysosomal degradation. It is a key enzyme in granule serine proteases activation in cytotoxic T lymphocytes and natural killer cells (granzymes A and B), mast cells (tryptase and chymase), and neutrophils (cathepsin G and elastase) by removing their N-terminal activation dipeptides.
Cathepsin D, lysosomal aspartic protease (EC 3.4.23.5), is essential for proteolysis of proteins regulating cell growth and tissue homeostasis. It is involved in breast and prostate cancer.
Cathepsin K is a cysteine protease (EC 3.4.22.38) which is selectively and abundantly expressed in osteoclasts (cells which break down bone). It is thought to play a role in resorption in bone remodeling and inhibitors of cathepsin K can reduce bone resorption in disorders such as osteoporosis.

Cathepsin inhibitors: compounds inhibiting the effects of cathepsins and so having modulating effects on bone metabolism and cancer. Examples include BML-244 (a potent and selective inhibitors of cathepsin K), CA-074 (a potent, selective and irreversible inhibitor of cathepsin B), calpeptin (inhibits cathepsins L and K) and leupeptin (inhibitor of cathepsin B).

Caudal: relating to the tail or a position near it.

Caudate nucleus: an elongated curve-shaped mass of grey matter in the basal ganglia which forms part of the corpus striatum and the most medial of the four basal ganglia. Impaired  caudate function is related to Parkinson's and Huntington's diseases and other motor disorders as the caudate nucleus is partly responsible for body movement and coordination.

Causalgia: a burning pain in a limb usually along the course of a peripheral nerve.

C_b: the concentration of drug in blood usually given in units of mg/l or mM.

Cbd: the concentration of bound drug in blood usually given in units of mg/l or mM.


CBR:central benzodiazepine receptor

C-C chemokine: a type of chemokine.

CC: cytotoxic concentration, the concentration of a drug which kills cells.

CCBS: calcium channel blockers

CCI: chronic constriction injury

CCK: cholecystokinin

C_D: the concentration of drug in dialysate usually given in units of mg/l or mM.

CD: controlled drug

CDJ: choledocho-duodenal junction

CDK:cyclin-dependent kinase

CDS: clonidine-displacing substance

CEC: chloroethylclonidine

Cefadroxil: an orally active, first generation semi-synthetic cephalosporin antibiotic with a long duration of action. It is used clinically for the treatment of urinary tract infections, respiratory infections and soft tissue infections. It was first patented in 1967.

Cefotaxime: a third generation cephalosporin used clinically to treat gram-positive, gram-negative bacterial infections and Staphylococcus aureus infections. Indications include gonorrhoea and meningitis.

Ceftriaxone: a third generation cephalosporin used clinically to treat gram-positive,  gram-negative bacterial infections and Staphylococcus aureus infections. Indications include gonorrhoea and the prophylaxis of meningococcal meningitis.

Ceiling: the maximum biological effect that can be produced by a drug regardless of the dose. The maximum effect observed may be less than the maximum response possible by the target tissue and less than the maximum response which can be induced by another drug of greater intrinsic activity. The ceiling is analogous to the maximum reaction velocity of an enzymatic reaction when the enzyme is saturated with substrate. The 'opposite' of ceiling dose is threshold dose.

Cell adhesion: the adhesion of cells to each other either between like cells or completely different cells or between cells and the extracellular matrix (ECM). Cell adhesion is an important process in many pathological processes such as tumour development and metastasis, for the normal function of migratory cells such as white blood cells, for the normal development of the embryo and morphogenesis, in viral and bacterial interactions with human cells and  in holding synapses together. These cell-cell and cell-ECM interactions are mediated by cell adhesion molecules.

Cell adhesion molecules: glycoproteins present on the surface of a wide variety of cells which are responsible for intracellular adhesion and between cells and with the extracellular matrix. They include cadherins, integrins and selectins.

Cell cycle inhibitor: any drug which inhibits the cell cycle and so stops cells from replication. These drugs are typically used to treat cancer and can be classified according to their effects of the cell cycle. Phase-specific agents which include vinca alkaloids, cytarabine and fluorouracil act in a specific phase of the cell cycle which is S in the case of these drugs. Cycle-specific agents act at all stages of the cell cycle and have little or no effect on non-replication cells. Examples include alkylating agents, cisplatin and dactinomycin. Cycle non-specific agents which act on cell whether they are actively replicating or not. Examples include nitrosoureas and bleomycins.

Cell lines: varieties of cells which are a permanently established and which will proliferate indefinitely under the right environmental conditions. They differ from cell strains in that they have been immortalized so can be stored frozen and the same cell line used repeatedly and reproducibly in experiments. Cell lines are used for a broad range of research but a typical application is their use in determining the potency of anticancer drugs. In this case cell lines such as P388, a mouse lymphocytic leukemia cell line, and .Jurkat cells which are human T-cell leukemia cells.

Central nervous system (CNS): the part of the body encompassing the spinal cord and the brain.

Central nervous system depressants: drugs which make brain activity slow down. they are used clinically to treat disorders such as anxiety, muscle tension, insomnia, pain, stress, panic attacks and seizures. Examples include a wide range of compounds including alcohol, narcotics, barbiturates, benzodiazepines, chloral hydrate, buspirone and zolpidem. CNS depressants often act via activation of GABA.

Central nervous system stimulants: drugs which speed up brain activity. They are used clinically to treat narcolepsy, neonatal apnea, attention-deficit hyperactivity disorder and to decrease appetite in cases of obesity. Examples include methylphenidate, dextroamphetamine, benzphetamine, phentermine and diethylpropion.

CETP: cholesterol ester transfer protein

Cephalosporins: a family of antibiotics used to treat a wide range of bacterial infections. They were originally isolated from fungi of the genus Cephalosporium by Giuseppe Brotzu. They are chemically related to penicillins but the cephalosporin ring structure is derived from 7-aminocephalosporanic acid (7-ACA) while the penicillins are derived from 6-aminopenicillanic acid (6-APA) although both structures contain the basic β-lactam ring. Since they were first developed successive generations have been produced. Examples include the 1st generation cephalosporins such as cefadroxil, cephalothin, cephalexin and cephadrine, 2nd generation drugs such as cefuroxime, cefamandole, cefoxitin and cefprozil, 3rd generation drugs such as cefdinir, cefixime, ceftazidime and cefaperazone. They are used clinically against a broad range of infections such as pneumonia, tonsillitis, bronchitis and gonorrhoea. The part of some cephalopsorins derived from the 7-aminocephalosporanic acid moiety is shown in blue.



Cephalosporinase: see β-lactamase.

effects of anticancer drugs. Examples include phenoxodiol, suramin, topotecan (a topoisomerase I inhibitor) and valspodar (which inhibits the efflux of anticancer compounds from tumor cells).

Chemotaxis: the movement of cells or organisms in response to the presence of specific chemicals (chemotactic factors). Chemotaxis is an important process in inflammation where chemotactic factors attract leucocytes along a concentration gradient of to a site of tissue injury or a wound where they then kill microorganisms or facilitate tissue repair.

Chemotactic factors: also known as chemotaxins and chemoattractants,  compounds and often peptides which that attract or repel cells to a particular site. The cells usually follow a chemical gradient towards the cell producing them (chemokinesis). These factors refer particularly to factors released as a result of tissue injury, invasion, or immunologic activity and which attract leukocytes, macrophages or other cells to the site of infection or injury. Chemotactic factors are derived from three general sources: bacterial (N-formylated peptides), plasma proteins (such as compliment, fibrinopeptides, kallikrein and plasminogen activator) and cells (such as cytokines, TGF-β, platelet activating factor, leukotrienes). Generally speaking, chemotactic factors are pro-inflammatory and attract cells to the sites of inflammation.

Chemotherapy: the use of drugs in the treatment of disease but usually restricted to the treatment of microbial infections and cancer. The term was first used by Paul Ehrlich around 1900 when he referred to the killing of microorganisms with chemicals.

Chemotherapeutic index: also known as the therapeutic index, the ratio of maximum tolerated dose of a drug to the minimum dose effective against microorganisms or cancer cells. This term was originally defined by Paul Ehrlich.

Chemotransmitter: another name for neurotransmitter.

Cheng-Prussof method: a method to calculate the inhibition constants (K_i) for the inhibition of binding of a competitive agonist at its receptor site. The Cheng-Prussof equation is:

(K_i = IC₅₀/(1+(L/K_D))

where L is concentration of radioligand, IC₅₀ is the concentration of drug needed to achieve 50% of maximal effect, and K_D is the affinity of the radioligand for the receptor. There are several variants to the Cheng-Prussof equation notably the Leff-Dougall variant.
Leff P and Dougal IG. Further concerns over Cheng-Prussof analysis. Trends Pharmacol Sci (1993) 14(4);110-2
Cheng Y and Prusoff WH. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol (1973) 22; 3099-3108

Chi-squared test: a statistical test to determine if an observed distribution of values or results differs from the expected distribution.
Pearson's Chi-squared for independence (the most commonly used Chi-squared test) determines if an observed distribution of values or results differs from the expected distribution and is calculated by assuming that the null hypothesis is true, ie that there is no difference in the mean values of these distributions. This test assumes that the observations are independent of each other and are identically distributed.

Chick dorsal root ganglia: a nodule on a dorsal root of a spinal nerve which contains cell bodies of afferent spinal nerves the axons of which convey somatosensory information. These ganglia are used to determine the effects of drugs on ganglia and to study the physiology of neurones.
Gottmann KD et al. Development of inward currents in chick sensory and autonomic neuronal precursor cells in culture. J Neurosci (1988) 8:3722–3732

Chick embryo chorioallantoic membrane (CAM): an extra-embryonic membrane formed on about day 4 of incubation by fusion of the chorion and the allantois. It mediates gas exchanges with the extra-embryonic environment and has a very thick capillary network which forms a continuous surface in direct contact with the shell. It is used to determine the effects of drugs on the promotion and inhibition of angiogenesis. The major disadvantage of the CAM preparation is that it contains a well-developed vascular network and vasodilation caused by its manipulation can be hard to distinguish from the effects of a drug being tested. Other preparations used to investigated angiogenesis include hamster cheek pouch, the rabbit ear chamber, the dorsal skin and air sac and the iris and avascular cornea of the rodent eye.

Chimeric receptor: a form of receptor.

Chinchilla: a small rodent sometimes used in the modeling of middle ear pneumococcal infection (otitis media).

Chiral: a property of a molecule where it is not superimposable on its mirror image. Chirality is of extreme importance as different enantiomers often have different pharmacological properties.

Chitin: nitrogenous polysaccharide linear polymer and a major component of arthropods, diatoms, higher plants and fungal cell walls. Chitin is not present in mammalian cells.

Chitin synthase: an enzyme (EC 2.4.1.16) which produces chitin from UDP-N-acetylglucosamine and an enzyme essential in fungal cell wall synthesis.

Chitin synthase inhibitors: a class of antifungal compounds which inhibit chitin synthase preventing fungal cell wall production. Examples include nikkomycins and polyoxins (both fermentation products of Streptomycetes) which act as substrate mimics for chitin precursors and competitively inhibit chitin synthase.

Chloralose: an anaesthetic used for laboratory animals such as cats and dogs. It must be injected intravenously or intraperitoneally and may cause convulsive muscle spasms during onset of anaesthesia. It also caused depression of the neuromuscular junction activity and so is not suitable for all experiments. The duration of chloralose anaesthesia is long when cats and dogs are given doses of 80 to 100 mg/kg.

Chloramphenicol: an broad-spectrum antibiotic originally isolated from cultures of Streptomyces venezuelae in 1947. As it has a relatively simple chemical structure it was synthesized soon after in 1949 and was the first antibiotic to be produced commercially. It does not fall into any established chemical class of antibiotic but is a potent inhibitor of bacterial protein synthesis with almost no effects on other metabolic processes. It binds to the 50S subunit of bacterial ribosomes and prevents transpeptidation, ie elongation of peptide chains. It is bacteriostatic for most organisms and bactericidal for a few including Haemophillus influenzae. Although more toxic than many of its modern counterparts, is still used to treat gram-positive bacterial infections, gram-negative bacterial infections and rickettsiae.

Chloride channels: a family of about 9 cell membrane channels which control the influx and efflux of Cl^- ions into and out of cells. They are important in the regulation of cellular pH, volume homeostasis, cell migration, organic solute transport as well as cell proliferation and differentiation. Faulty chloride channels are associated with various congenital diseases including Myotonia Congenita (Thomsen's disease), Barter's Syndrome, Dent's Disease and cystic fibrosis.

Chloride channel activators: compounds which open chloride channels. Examples include lubiprostone, the first chloride channel activator approved in the US for the treatment of chronic idiopathic constipation in adults. It acts by increasing fluid secretion into the intestinal tract by locally activating specific ClC-2 chloride channels on cells lining the small intestine. Other chloride channel activators are being developed for the treatment of cystic fibrosis, an autosomal recessive genetic disorder which causes abnormal electrolyte transport in a variety of epithelial cells especially in the lung, pancreas and testes. In this disease there is a genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR). Cystic fibrosis is a life-threatening disease which affects the lungs and pancreas by clogging them with thick, sticky mucus and impairing their function particularly causing breathing difficulties and giving rise to lung infections. Find more on cystic fibrosis in Wikipedia.

Chloride channel blockers: compounds which block chloride channels. Examples include chlorotoxin (death stalker scorpion toxin from Leiurus quinquestriatus), picrotoxin (a plant alkaloid and a non-competitive GABA_A antagonist from Cocculus indicus and Anamirta cocculus) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid

Chlorisondamine: a very long-lasting nicotinic antagonist used primarily as a ganglionic blocker and pharmacological tool. It has been used as an antihypertensive. Blockade can last several weeks.

Chlormezanone: an anxiolytic and skeletal muscle relaxant (2-(4-chlorophenyl)tetrahydro-3-methyl-4H-1,3-thiazin-4-one 1,1-dioxide). It is a non-benzodiazepine muscle relaxant the clinical used of which was discontinued worldwide in 1996 due to serious and rare cutaneous reactions (toxic epidermal necrolysis).

Chlorotoxin: a 36 amino acid basic peptide obtained from the death stalker scorpion (Leiurus quinquestriatus) which has been use as a pharmacological tool as it blocks small-conductance chloride channels.

Chloroethylclonidine (CEC): a site-directed alkylating agent and irreversible antagonist of α_1B- and α_1D-adrenoceptors.

Chloroquine: an antimalarial compound used clinically in the prophylaxis and treatment of infections caused by Plasmodium malariae and similar parasites. Chloroquine is also used to treat active rheumatoid arthritis and systemic and discoid lupus erythematosus.

Chlorpromazine: a classical (also known as typical) phenothiazine antipsychotic compound used clinically to treat schizophrenia particularly in violent patients, psychoses, mania, psychomotor agitation, excitement and violent and impulsive behaviour.

Chlorpropamide: a long-acting sulphonylurea used clinically as an oral hypoglycaemic in the treatment of type 2 (non-insulin dependent) diabetes. Like all sulphonylureas, it stimulates insulin secretion by the B cells in the pancreas probably by binding to high-affinity receptors for sulphonylureas present of the ATP-sensitive potassium channels in B-cell plasma membranes.

Cholecystokinin (CCK): also known as pancreozymin, a hormone originally thought to contain 33 amino acids but actually  comprising a varying number of amino acids depending of post-translational modification and varying in length from 58 amino acids (CCK-58) to 4 amino acids (CCK-4). C-terminal amino acids 4-10 are required fo its activity. All these peptides come from prepro-CCK, a 115 amino acid precursor. It is present in the mucosa of the small intestine brain and pancreas. CCK stimulates contraction of the gallbladder, causes release of bile and is responsible for the digestion of lipids and proteins. CCK causes the release of digestive enzymes and bile from the pancreas and gallbladder. Its release is caused by ingestion of lipids and fatty acids. In the brain, CCK causes nausea and anxiety and has a weak effect on decreasing the desire to eat.

Cholecystokinin receptors: a family of two receptors for cholecystokinin, CCK-A (correctly known as CCK₁) and CCK-B (correctly known as CCK₂). CCK-₁ receptors are present in the pancreatic acinar cells, the gallbladder, on adenohypophysis cells and on inhibitory neurons in the lower oesophageal tract. CCK-₂ receptors are present in the cerebral cortex and central nervous system. CCK receptors may play a role in food intake, satiety, depression and anxiety.
Noble F et al. International Union of Pharmacology. Structure, Distribution, and Functions of Cholecystokinin Receptors. Pharmacological Reviews (1999) 51(4); 745-781
http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1281

Cholecystokinin receptor agonists: compounds which agonise CCK receptors. Examples include caerulein, the CCK-₂ receptor agonist BOC-CCK-4, the CCK-₂ selective compound BC264 and the CCK-₁-selective CCK-4 analogue, A71623. They are used as pharmacological tools in determining the function of these receptors. CCK agonists may be of use in treating eating disorders. GI181771X (an oral CCK₁ agonist) is being investigated for its effects on weight loss.

Cholecystokinin receptor antagonists: compounds which block the effects of CCK and its agonists at CCK-₁ and CCK-₂ receptor sites. Examples include MK-329 (also known as L-364,718 and devazepide and a potent CCK-₁ receptor antagonist), proglumide and benzotript (both non-selective), the non-peptide CCK-₂ receptor antagonist LY288513 and YM022 (a potent ans selective CCK-₂ antagonist). CCK antagonists are being used in the search for drugs to treat eating disorders as both devazepide and L-365,260 (a potent CCK-₂ antagonist) are known to increase food intake and block the delay the onset of satiety in experimental animals CCK-₂ antagonists may be of use in treating depressive illness.

Choledocho-duodenal junction (CDJ): a preparation usually in cats and dogs used to study autonomic innervation and the control of sphincters regulating bile secretion.

Cholelitholytics: compounds used to dissolve gall stones. Examples include ursodeoxycholic acid.

Choleretics: substances which stimulates the formation of bile. Examples include ursodeoxycholic acid and cholestyramine.

Cholestasis: the stoppage or suppression of bile production. Cholestatics are compounds which inhibit bile production and flow.

Cholesterol ester transfer protein (CETP): a protein which mediates triglyceride and cholesteryl ester transfer between lipoproteins and is important in cholesterol homeostasis because it participates in the conversion of HDL-cholesterol to LDL-cholesterol. High plasma levels of CETP are related to low HDL cholesterol levels and this is a strong risk factor for coronary artery disease.

Cholesterol ester transfer protein inhibitors: compounds which inhibit cholesterol ester transfer protein and which inhibit lipid metabolism. They increase plasma HDL cholesterol levels and inhibit the progression of atherosclerosis in experimental animals and so are being developed to treat hyperlipidemia. Examples include JTT-705 and torcetrapib (also known as CP-529414).

Cholestryamine: also known as colestyramine, an anion-exchange resin and bile acid sequestrant which is not absorbed in the gut. When taken orally it sequesters bile acids in the gut to prevent their absorption and enteroheaptic recirculation thus inhibiting the absorption of exogenous cholesterol and increased incorporation of cholesterol into bile acids in the liver. It has been used clinically in the treatment of hypercholesterolaemia.

Choline: a precursor of acetylcholine which it forms after accepting an acetyl group from acetyl CoA in cholinergic neurons.

Choline carrier: a membrane carrier system which reuptakes choline into cholinergic nerve terminals after it has been split from acetylcholine by acetylcholinesterase in the synaptic cleft.

Choline transport: an active process whereby choline is taken up by cholinergic neurons for incorporation into acetylcholine by a choline carrier.

Choline transport inhibitors: compounds which inhibit the active process of choline transport. Inhibitors include hemicholiniums such as hemicholinium-3 and triethylcholine.

Choline acetyltransferase (CAT): also known as choline acetylase, an enzyme (EC 2.3.1.6) which catalyzes the acetylation of choline to form acetylcholine. This enzyme is synthesized by the ribosomes in the neuron cell body and is transported to the axon terminal (where acetylcholine synthesis takes place) by axoplasmic flow.

Choline uptake enhancer: compounds which increase the uptake of choline by cholinergic neurons. Examples include MKC-231. Choline uptake enhancers may be of use as cognition enhancers.

Cholinergics: also known as directly acting cholinoceptor stimulants, drugs which agonize nicotinic and muscarinic receptors.

Cholinergic crisis: a disorder in which there is too much cholinesterase inhibition which can sometimes occur is disorders such as myasthenia gravis. The symptoms of cholinergic crisis include muscle fasciculation, sweating, excessive salivation and  constricted pupils. This disorder can be treated by stopping anticholinesterase administration and giving atropine.

Cholinesterases: a group of serine hydrolases which hydrolyze acetylcholine to choline and acetate to terminate the actions of this transmitter. Two distinct types exist, ie acetylcholinesterase and butyrylcholinesterase.
Acetylcholinesterase (AChE) (EC 3.1.1.7) also known as specific cholinesterase or true cholinesterase, is found bound to the basement membrane of the synaptic cleft at cholinergic receptors and is associated with motor endplates. Soluble AChE is also present in nerve terminals where it appears to function in the regulation of free acetylcholine concentrations.
Butyrylcholine (BChE) (EC 3.1.1.8) also known as nonspecific cholinesterase or pseudocholinesterase.
Propionylcholinesterase has been isolated from bean and heart tissue of some animals but has no function in humans.

Cholinesterase inhibitors: also known as indirectly acting cholinoceptor stimulants, these compounds inhibit cholinesterase thereby inhibiting the metabolism of acetylcholine.

Cholinesterase reactivators: compounds which can reactivate cholinesterases after it has been inhibited by anticholinesterases. They pull the enzyme inhibitors away from its binding site, an observation which followed experiments in the early 1950s showing that hydrxoylamine and hydroxamic acids could dislodge organophosphorus inhibitors from cholinesterase, then remove phosphate groups from the enzyme. They are used in the treatment of organophosphorus poisoning and are important as antidotes in nerve gas poisoning which is a consequence of chemical warfare. Examples include pralidoxime, obidoxime and trimedoxime.

Cholinoceptors: receptors sensitive to acetylcholine and widely spread throughout the peripheral and central nervous systems. They are divided into muscarinic and nicotinic. Nicotinic receptors are ligand-gated ion channels and muscarinic receptors are G protein-coupled receptors.

Cholinomimetic: relating to compounds with actions similar to those of acetylcholine. Examples include tacrine, an acetylcholine release enhancing agent.

Chloroacetylocholine: a reversible inhibitor of choline acetyltransferase which has a very short half-life due to rapid hydrolysis. Other halogenated derivatives of acetylcholine also inhibit this enzyme.

Chromogranins: a group of acidic polypeptides which make up the soluble protein constituents of secretory granules found in chromaffin cells of the adrenal medulla and also widely distributed in endocrine tissues and tumour cells.

Chronic constriction injury (CCI): a form of nerve injury caused by a ligature tied around a nerve such as the sciatic nerve in a rat and used as a standard model for inducing neuropathic pain.

Chung's model: a model of chronic neuropathic pain comprising tight ligation of one of the two spinal nerves of the sciatic nerve. It is a general model of neuropathic pain and is a good model for in vitro use.
Kim S and Chung J. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain (1992) 50; 355-63

CIA: collagen-induced arthritis.

Ciclosporin (cyclosporin): a group of over 10 lipophilic cyclic polypeptide immunosuppressant, antibiotic and antifungal compounds originally isolated from the fungus tolypocladium inflatum from which ciclosporin A was isolated in 1972. The most common is ciclosporin A which acts specifically upon T cells and is used clinically as an immunosuppressant following organ and bone marrow transplantation and for the prophylaxis and treatment of graft vs. host disease. Ciclosporin A is a calcineurin inhibitor.

Cilastatin: en enzyme inhibitor which is given together with imipenem (a carbapenem antibacterial) to inhibit its breakdown in the kidney and so prolong its half-life. Cilastatin inhibits renal dehydropeptidase-1.

Ciliary ganglion preparation: a preparation of ciliary muscle typically from the eye of a domestic fowl (chick) which has purely cholinergic innervation and originally developed by Pilar et al as a model cholinergic system.

Ciliary neurotrophic factor (CNTF): a cytoplasmic protein and neurotrophic factor which promotes the survival of various neuronal cell types and may play an important role in injury response in the nervous system. It is also important in muscle development.

Cilostamide: a cyclic nucleotide and selective phosphodiesterase 3 inhibitor.

Cilostazol: a quinolone derivative and inhibitor of phosphodiesterase 3 It is used clinically to treat intermittent claudication as it is a vasodilator.

Cimetidine: a first-generation histamine receptor antagonist developed by rational drug design and the first one of its kind marketed back in 1976 for the treatment of gastric and duodenal ulcers. It reduces gastric acid output by blocking H₂ receptors as gastric acid output is mediated by histaminergic neurons. Cimetidine is still used to treat benign gastric and duodenal ulcer, reflux oesophagitis and Zollinger-Ellison syndrome although proton pump inhibitors are usually the drugs of choice in reducing gastric acid output.

Cinchona alkaloids: a group of about 30 alkaloids present in the bark of some tropical trees particularly Cinchona succiruba (the cinchona tree). Examples of cinchona alkaloids include quinine (used clinically to treat malaria and nocturnal leg cramps), cinchonine and cinchonamine.

Cinnarizine: a peripheral vasodilator used clinically to treat peripheral vascular disease and Raynaud’s syndrome and to treat vestibular disorders such as vertigo, tinnitus, nausea and vomiting. It is an antihistamine and calcium channel blocker (where it is 1000 times more effective in blocking slow calcium channels in vascular smooth muscle than in the myocardium) and is known to cause drug-induced parkinsonism.

CINV: chemotherapy-induced nausea and vomiting

CIR: controlled ileal release, a dosage form for drugs used to treat the terminal ileum and ascending colon for disorders such as Crohn’s disease, ulcerative colitis and irritable bowel syndrome.

Cirazoline: a non-subtype selective α₁-adrenoceptor agonist.

Ciprofloxacin: a fluoroquinolone antimicrobial used clinically to treat both gram-positive and gram-negative infections but more potent against the latter. It is used to treat eye infections and corneal ulcers.

Cisapride: a gastroprokinetic which increases gut motility by stimulating acetylcholine release in the myenteric plexus in the upper gastrointestinal tract. It has been used to treat reflux oesophagitis and gastric emptying disorders.

Cisplatin: a water-soluble, platinum-containing anticancer compound synthesized as the first of a series of cytotoxic organoplatinum compounds. It is used clinically to treat metastatic germ cell cancers and cancers of the bladder, lung, upper gastrointestinal tract and ovaries. It acts by causing intrastrand crosslinking in DNA which causes breakage of hydrogen bonds between guanine and cytosine bases leading to localized denaturation of the DNA chain.

Citicholine: also known as CDP-choline and citidine(5')-diphosphocholine, an inhibitor of phospholipase A₂ activation, a cerebral vasodilator and a neuroprotectant under hypoxic and ischemic conditions in animals.

CL316243: a selective β₃-adrenoreceptor agonist used as a tool to investigate the function as well as tissue and species distribution of this adrenoceptor subtype.

CL: the total clearance of a drug from plasma usually given in units of l/hr.

CL_b: the total clearance of drug from blood usually given in units of l/hr.

CL_b,D: the dialysis clearance based on the concentration of drug in blood usually given in units of l/hr.

CL_b,H: the hepatic clearance of drug from blood usually given in units of l/hr.

Clarithromycin: a macrolide antibiotic which acts by inhibition of bacterial protein synthesis. It is used clinically to treat respiratory tract infections, mild to moderate skin and soft tissue infections, otitis media and in the eradication of Helicobacter pylori.

Clark AJ: a British pharmacologist who worked at University College London where he was one of the first people to describe the relationship between ligands, receptor occupation and the effects of receptor occupation. He wrote ‘Applied Pharmacology’ which was originally published in 1923.

Clark's theory: also known as occupancy theory.

Clastogen: a substance which cause breaks in chromosomes which result in the gain, loss, or rearrangements of chromosomal segments. Clastogens can be mutagenic and carcinogenic.

Claviceps alkaloids: ergot alkaloids

Clavulanic acids: a group of antibiotic obtained from Streptomyces clavuligerus  which includes clavulanic acid and its derivatives β-hydroxypropionyl calvulanic acid and clavam-2-carboxylic acid. The most important member is clavulanic acid which is a β-lactam but shows only weak inhibitory effects on bacterial cell wall transpeptidase. It markedly inhibits β-lactamases which are formed by gram-positive and gram-negative bacteria and can potentiate the effects of β-lactams which are normally inactivated by this enzyme. In this respect it acts like a suicide inhibitor.

Clearance (CL): a measure of the body's ability to rid itself of a drug. It is defined as the volume of blood, serum or plasma from which bound or unbound drug is completely removed per unit time. Clearance is measured in units of ml/minute and it is additive; the total clearance being the sum of renal clearance, metabolic clearance, biliary clearance etc. The values for CL will usually lie between less than 1ml/minute for a drug which extremely slowly cleared from the system to about 700ml/minute which is a theoretical maximum as this is the actual blood flow rate through the kidney. Renal clearance, which is probably the most important, is determined by active tubular secretion and passive reabsorption and it influenced by a multitude of factors such as age, disease state, pH of the blood. Several ‘types’ of clearance are known. Restrictive clearance is where clearance is restricted in some way such as by protein binding which restricts their metabolism as only unbound drug is eliminated each time is passes through the liver. An example of a drug showing restrictive clearance is diazepam because it is very highly protein bound (98-100% bound to plasma albumin). Drugs that are metabolized rapidly by the liver show non-restrictive clearance. Clearance is an extremely important measurement in pharmacokinetics as it directly affects the dose of a drug or the concentration of drug in an infusion fluid or dosage form which must be administered in order for the drug concentration in blood to be kept within its therapeutic range. It is also important as metabolic and excretory impairment such as seen in renal disease will markedly affect clearance values.

Clenbuterol: a substituted phenylethanolamine and selective β₂-adrenoceptor agonist (4-amino-3,5-dichloro-α-[[(1,1-dimethylethyl)amino]methyl]benzenemethanol) which has been used as an orally active and long-acting bronchodilator and as a tocolytic (to prevent premature labour). It also has anabolic effects and has been used illicitly by sportsmen and women because it can increase the rate and force of skeletal muscle contractions.

Clinical pharmacology: a branch of pharmacology which deals with the treatment of humans and animals with drugs in a clinical setting.

Clobenpropit: also known as VUF 9153, a potent H₃ histamine receptor antagonist. Since H₃ antagonists enhance neurotransmitter release it may be of use in the treatment of neurological and cognitive disorders. It may also be able to modulate vascular contractions in some tissues by inhibition of noradrenaline release from sympathetic nerve terminals. It is being used as a tool to elucidate the functions of H₃ receptors.
Barnes JC et al. Pharmacological activity of VUF 9153, an isothiourea histamine H₃ receptor antagonist. Eur J Pharmacol (1993) 250(1);147-152

Clofibrate: a fibrate and an antihyperlipidaemic (2-(4-chlorophenoxy)-2-methylpropanoic acid ethyl ester) used for the treatment of hyperlipidemia and ischemic heart disease. It is an ester and is rapidly hydrolyzed after absorption to form chlorophenoxyisobutyric acid which is responsible for its actions. Clofibrate causes a marked decrease in circulating VLDL levels, a small reduction in LDL and a small increase in HDL. Like other fibrates it stimulated lipoprotein lipase and so increases hydrolysis of triglyceride in chylomicrons.

Clomiphene (clomifene): a non-steroidal stimulant of ovulation used clinically to treat anovulatory infertility. It induces gonadotrophin release by oestrogen receptor modulation in the hypothalamus which inhibits the normal feedback mechanism and so increases gonadotrophin levels in the blood. This rise in gonadotrophins causes steroidogenesis and folliculogenesis resulting in ovarian follicle growth and an increase in the circulating level of oestradiol.

Clonazepam: a benzodiazepine used clinically to treat all forms of epilepsy and myoclonus status epliepticus.

Clonidine: a prototypical I₁ imidazoline receptor ligand (agonist) and α₂ adrenoceptor agonist which is used clinically to treat hypertension, migraine and menopausal flushing. It has also been used to treat heroin addiction.

Clonidine-displacing substance (CDS): see agmatine

Clonidine mydriasis: an animal model of mydriasis caused by the application of eyedrops containing clonidine and widely applied in preclinical research to characterize α_2-adrenoceptor antagonist actions of drugs.

Clopidogrel: an antiplatelet drug structurally related to ticlopidine and used clinically to prevent atherosclerotic events in peripheral arterial disease. Clopidogrel inhibits ADP receptors on platelets and inhibits thromboxane-mediated platelet aggregation.

Clostridial neurotoxins (CNT): a family of bacterial protein toxins obtained from the genus Clostridium and which include tetanus neurotoxin and several serologically distinct botulinum neurotoxins. These toxins block neurotransmitter release in nerve endings and thereby cause tetanus or botulism, respectively, any can cause death by respiratory failure. They are important causes of food poisoning, important as toxins in chemical warfare and used as pharmacological tools to study neurotransmission.
Schiavo G et al. Clostridial neurotoxins as tools to investigate the molecular events of neurotransmitter release. Semin Cell Biol.(1994) Aug 5; 221-9

Closylate: a USAN contraction for 4-chlorobenzenesulphonate and a pharmaceutical salt form of some drugs. Examples include thenium closylate, a nicotine-like quaternary drug used in veterinary medicine to treat nematodal infections.

Clozapine: a piperazinyl derivative and an atypical antipsychotic compound. It is used clinically to treat schizophrenia (including schizophrenia in Parkinson’s disease) in patients who are unresponsive to or intolerant of conventional antipsychotics. Clozapine is a D₄ dopamine antagonist but also binds to serotonin receptors.

CLP: cecal ligation and puncture

CM hamster: cardiomyopathic hamster, an animal model of hereditary cardiomyopathy.

CNTF: ciliary neurotrophic factor

C0: symbol denoting the (hypothetical) concentration of a compound in the plasma at the moment an instantaneous injection of a drug is given and which is assumed to be instantaneously distributed throughout the body so that it has reached its volume of distribution. C0 can be determined from a plot of log C against t (for a fist order decrease in C) or from a plot of C against t (for a zero order decrease in C) by, in both cases, extrapolating the line to zero time.

Co-agonist: an agonist releases at the same time as the principal agonist. An example is glycine which is released from glutaminergic neurons.

Coca: the dried leaves of the plant Ethroxylum coca and a source of cocaine, a recreational drug.

Coca alkaloids: alkaloids which are esters of ecgonine and pseudotropine and which belong to the tropane alkaloid family and include cocaine and tropacocaine.

Cocaine: a tropane alkaloid and the main alkaloid in leaves of the coca plant. It inhibits monoamine uptake in the brain and has local anaesthetic, euphoric and hallucinogenic effects because in increases the brain levels of dopamine, noradrenaline and serotonin. It is a drug of abuse and slang terms for cocaine include base, beam me up Scotty, Bernice, big C, blow, C, Carrie, Cecil, Charlie, cholly, cloud 9, Corine, crack, crystal, dream, dust, dynamite, nose candy, nuggets, parachute, paradise, rocks, sleigh ride, snow, stardust, wash rock, white cloud, white girl, white lady, white stuff and zoom.

Co-carcinogens: compounds which potentiate the activity of a carcinogen without themselves being carcinogenic. Co-carcinogens must be present at the same time as carcinogens to be effective and differ from tumour promoters which do not have to be present at the same time. Examples of co-carcinogens include catechol in tobacco smoke and alcohol.

Coccidiostats: compounds which partially inhibit or delay the development of coccidiosis, a protozoan infection found in animals and humans caused several different genera of coccidia. Examples include amprolium and nicarbazin which are used to treat coccidiosis particularly in chickens where this disease is prevalent but it also occurs in cattle, sheep, cats and dogs. These compounds are commonly mixed into feedstuff.

Codeine: also known as methylmorphine, an opium alkaloid ((5α,6α)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol) obtained from the opium poppy (Paparverum somniferum) and which can be prepared by methylation of morphine (the structures of morphine and codeine are shown below). It is an opioid receptor agonist with antitussive, analgesic and antidiarrhoeal actions and is more effective orally than morphine. It is a relatively non-addictive compound and is often used in conjunction with NSAIDs in non-prescription painkillers.



Coeliac (celiac) ganglion: also known as the solar plexus, the largest of the prevertebral sympathetic ganglia located on the superior section of the abdominal aorta on either side of the origin of the coeliac artery. This ganglion contains sympathetic neurons and unmyelinated postganglionic axons from it innervate the stomach, liver, gallbladder, spleen, kidney, small intestine and colon. It is used in pharmacology to study peripheral neurotransmission.

Coenzyme: a small molecule often a vitamin which is essential for the activity of an enzyme. The coenzyme usually increase the rate of reaction, act as carriers in the transfer of chemical groups and examples include nicotinamide adenine dinucleotide (NAD) and biotin.

Cofactor: atoms, groups of atoms and molecules which bind to enzymes altering their shape and making them functional. They act as ‘on-off’ switches for enzyme activation. 

Cognition enhancer: also referred to as smart drugs, drugs which improve cognition, ie perception, thinking and memory. Many drugs are claimed to enhance cognition and some such as AIT-082, nefiracetam and modafinil.

Cognitive disorder: neurological disorders which include delirium (a state of global cortical dysfunction seen as alterations in attention and cognition), dementia (disorders of memory impairment such as Alzheimer’s disease and Creutzfeldt-Jakob disease) and amnestic (isolated disturbances in memory) disorders. They can be caused by a variety of disorders including drug abuse, metabolic abnormalities, neuronal loss, trauma, cerebrovascular disease and infections.

Cohort study: a study in which patients who suffer from a specific disease or condition and/or who are receiving a particular treatment are followed over a period of time and compared with another group who are not affected by the disease or condition being investigated. Generally speaking, cohort studies are not as reliable as randomized controlled studies because the two groups being studied may show differences in terms of their cultural or habitual backgrounds. The main problem with cohort studies is that they often take a very long time to carry out since the disease or condition being studied has to be allowed time to develop.

Colcemid: a cell cycle inhibitor which arrests cells at metaphase. It depolymerizes microtubules and inhibits their formation. It also induces apoptosis.

Colchicine: a colchicum alkaloid obtained from bulbs of the meadow saffron (Colchicum autumnale) where it occurs as the glucoside (colchicoside). It is a potent inhibitor of the cell cycle because it binds to the β-tubulin dimer during spindle formation thus blocking assembly of microtubules and causing disassembly of existing tubules. It has been used in medicine for over 200 years and is used clinically for the prophylaxis and treatment of gout.

Colchicum alkaloids: a group of isoquinoline alkaloids present in only a few plants of the genera Lilaceae. The main alkaloids in this group are colchicine and demecolcine which are both antineoplastics.

Cold receptor: a type of receptor (CMR1) which is activated at low temperature.

Colestipol: a bile acid sequestrant and an anion-exchange resin used clinically to treat hypercholesterolemia. It acts by binding to bile acids thereby preventing their reabsorption. This in turn promotes liver production of bile acids from cholesterol and the resultant increase in LDL-receptor in the liver increases the clearance of LDL-cholesterol.

Collagen: an extracellular protein which is an important component of connective tissue as it gives it strength and flexibility (accounting for up to 35% of the total protein content of mammals). It is biosynthesized by fibroblasts as a precursor, procollagen, and undergoes crosslinking during its formation which contributes to its strength.

Collagenase: a proteolytic enzyme and metalloprotease capable of degrading native collagen. It plays an important role in connective tissue disease.

Coloboma mouse: a hyperactive mutant mouse which responds to drugs which are used to treat attention deficit hyperactivity disorder such as d-amphetamine and atomoxetine. Amphetamine normalizes this hyperactivity in coloboma mice but induces hyperactivity in normal mice.

Colonic distension test: also known as colorectal distension test, a test for the effects of analgesics on visceral pain in which the rectum and distal colon of a rat, for example, are distended with constant pressure using a balloon. This test is used in conscious animals and mimics a natural but painful stimulus. Analgesics lower the animal’s sensitivity to pain.
Gebhart GF, Ness TJ. Central mechanism of visceral pain. Can J Physiol Pharmacol. (1991) 69; 627-634

Compartment: a tissue or fluid-filled ‘space’ within the body in which a drug becomes distributed after administration. Compartmentalization of drugs occurs because they show differences in their distribution according to their physicochemical characteristics such as lipid solubility and charge. A compartment is usually defined physiologically and/or anatomically and can be large such as the intravascular compartment which implies whole blood in every vessel or small such as the kidneys. When discussing distribution and excretion of a drug it is convenient to refer to one- and two-compartment models.

Competition assay: an assay to determine the potency with which a competing ligand (which may be an agonist or antagonist) and another competing ligand bind to a receptor.

Competitive antagonism: a form of drug antagonism.

Compliance: in drug therapy, the extent to which a patient or a volunteer actually takes drugs as prescribed. Drugs with many side effects show low compliance while those with few side effects or those considered to be essential to life such as anticancer agents and immunosuppressants show high compliance. Vascular compliance is a measure of the distensibility of a blood vessel and is a function of the change in volume per unit change in pressure.

Compound 48/80: a polymer which causes the degranulation of mast cells and release of histamine. It is used experimentally to test compounds which inhibit histamine release.

COMT: catechol-O-methyltransferase

Conantokins: a family of naturally occurring conopeptides (comprising 17-27 amino acids) from Conus (a genus of predatory cone snails) venoms. They are selective antagonists at the polyamine site of NMDA glutamate receptors. They have analgesic and neuroprotectant effects. In young mice conantokins have sedative effects but in older mice they induce hyperactivity.

Concentration-response curve: a form of dose-response curve.

Conditioned taste aversion (CTA): a form of associative learning and classical conditioning in which an animal tries to avoid a taste that has been previously associated with as unpleasant stimulus.

Conformer: a stereoisomer which is characterized by a conformation corresponding to a distinct potential energy minimum.

Congeneric series: a series of structurally related compounds which vary primarily only by their substituents. For example, benzene, phenol and aniline would be a congeneric series.

Congeners: one of many variants or configurations of a common chemical structure.

Congenic animal: an inbred strain that is genetically identical to another except at a one or more specified genetic loci. Their known genetic differences are expressed against the same genetic background. Congenic strains can be produced by out-breeding a strain and then eliminating the background by many generations of backcrosses while maintaining the desired genetic differences by careful selection of the progeny. They are used experimentally because they share phenotypic and genotypic characteristics with humans but have a greatly simplified genetic background.

Conotoxins: peptide neurotoxins from marine, fish-hunting snails of the genus Conus. ω-Conotoxin inhibits ACh release from cholinergic neurons by inhibiting voltage-activated entry of Ca²⁺ into presynaptic neurones. α-Conotoxin inhibits postsynaptic ACh receptors and μ-conotoxin inhibits the generation of muscle action potentials. These toxins are used as pharmacological tools.
Armishaw CJ, Alewood PF. Conotoxins as research tools and drug leads. Curr Protein Pept Sci (2005) Jun 6(3); 221-40

Consomic strain: also called a chromosome substitution strain, an inbred strain of animal commonly rat or mouse which contains a single entire chromosome from another strain Two strains of animal are consomic when they differ by one complete chromosome pair. See http://www.rgd.mcw.edu/nomen/rules-for-nomen.shtml on the rules of naming strains of rats and mice.

Contortrostatin: a component of the venom of southern copperhead snake (Agkistrodon contortrix contortrix) and a disintegrin. It binds to integrins on the surface of cancer cells and inhibits tumour growth and metastasis where it appears to block several steps in metastasis and may also have angiogenesis inhibiting actions.

Contraceptive: a device or substance used to prevent pregnancy occurring. Apart from devices preventing the physical transfer of semen into the uterus such as condoms and caps most contraceptives are chemical contraceptives.

Contract research organization (CRO): a usually private company which carries out toxicity, pharmacology testing and clinical trials of new chemical entities on behalf of the major drug-developing companies.

Contragestational agent: a substance which inhibits implantation or interrupts pregnancy after implantation of a fertilized egg. These include abortifacients and the morning-after pill.

Contraindication: a reason and usually an already existing disease state that makes it inadvisable to prescribe a particular drug or treatment.

Contralateral: situated on or pertaining to opposite sides. The synonym is ipsilateral.

Controlled drug (CD): any drug whose manufacture, supply and use is controlled by the Misuse of Drugs Act 1971 in the UK. They tend to be drugs of abuse and are divided into classes. Class A drugs include cocaine, heroin, LSD, ecstacy, morphine, pethidine and phencyclidine. Class B drugs include oral amphetamines, barbiturates and codeine while Class C drugs include cannabis, pemoline and anabolic steroids.

Convulsant: a compound which induces convulsions. Examples include bicuculline.

Copenhagen rat: a strain of rat first developed in 1921 which shows a high incidence of spontaneous thymus tumors. Transplantable tumors IRS 4337 and R3327 prostate adenocarcinoma will grow in this strain and it has been used as a model of human prostatic cancer.

Copper sulphate: a compound used in combination with radiation to induce vomiting in experimental animals in order to test the effects of antiemetics.

Coronary artery ligation model: an animal model of heart disease such as congestive heart failure and myocardial infarction in which the left anterior descending coronary artery is ligated with thread or a clip to starve the coronary muscle of blood, nutrients and oxygen. After a while cardiac parameters such as ejection fraction and left ventricular function and size alter as necrosis of the coronary muscle develops and eventually heart failure develops. This model is used to investigate the effects of drugs on cardiac function. This is a commonly used model although suffers the disadvantages of high mortality and marked variations in infarct size and cardiac dysfunction.

Coronary ligation-reperfusion model: an animal model of arrhythmias in which the left anterior descending coronary artery is ligated with thread or a clip to the point where cardiac muscle damage develops and the ligature is then removed to allow the heart to function with a damaged left ventricular muscle. Arrhythmias develop in this model which is used to investigate the effects of drugs on cardiac arrhythmias.

Corneal micropocket assay: a model of angiogenesis and a method to determine the effects of drugs on blood vessel formation. Typically, an incision is made in the cornea of a rat or rabbit and an angiogenic substance such as basic fibroblast growth factor is inserted into this pocket to promote angiogenesis. Angiogenesis inhibitors are then applied to the cornea and observed under a microscope to see the effects the drug may have of capillary growth. This assay has the advantages that it is reproducible, is economical and has rapid turnaround times.

Corticosteroids: a family of drugs that include cortisol, an adrenal hormone found naturally in the body, as well as synthetic analogues. Though natural and synthetic corticosteroids are both potent anti-inflammatory compounds, the synthetic derivatives are more potent. Oral formulations of corticosteroids are used to treat numerous autoimmune and inflammatory conditions, including asthma , bursitis, Crohn’s skin disorders, tendinitis and ulcerative colitis. They are also used to treat severe allergic reactions and to prevent rejection after organ transplant. They may be used orally, eg cortisone, prednisone and triamcinolone, they may be inhaled, eg  beclomethasone, budesonide and fluticasone or applied topically, eg alclometasone, clobetasol and dexamethasone.

Corticotropin: also known as adrenocorticotropic hormone (ACTH), a 39 amino acid hormone produced by the anterior pituitary gland which stimulates the adrenal cortex to release cortisol.

Corticotropin analogues: analogues of corticotropin (ACTH) which are used to diagnose functional disorders in the adrenal cortex and have been used in the treatment of adrenal cortex insufficiency, inflammation and Crohn’s disease and rheumatoid arthritis. Examples include tetracosactide and alsactide.

Corticotropin-releasing hormone (CRH): originally called corticotropin-releasing factor (CRF) and also known as corticoliberin, a 41 amino acid polypeptide hormone and neurotransmitter. It causes the release of corticotrophin from the anterior pituitary gland and stimulates the release of endorphin and dynorphin from rat pituitary, stimulates the synthesis and release of pro-opiomelanocortin and stimulates its degradation to form ACTH in the adenohypophysis and placenta. CRH increases the levels of corticosterone, aldosterone and 18-hydroxycorticosterone in the plasma via stimulation of ACTH release.

Corticotropin-releasing factor receptors: a family of receptors which mediate the effects of corticotrophin-releasing factor and include CRF₁, CRF_2a and CRF_2b receptors. CRF₂ receptors may mediate muscular disorders such as muscular dystrophy.
See http://www.iuphar-db.org/GPCR/IntroductionDisplayForward?chapterID=1321

Corticotrophin-releasing factor receptor agonists: compounds which agonise CRF receptors. Examples include CRH, urocortin and sauvagine. CRH agonists may be of use in the treatment of pain such as that related to cancer. CRH₁ agonists may act centrally as anxiolytics and CRH₂ agonists may have analgesic anc anxiolytic actions.

Corticotrophin-releasing factor receptor antagonists: compounds which block the actions of CRH at CRH receptor sites. Examples include antisauvagine-30 which is a potent, selective and competitive antagonist st CRH₂ sites and astressin which is an antagonist at CRH₁, CRH_2a and CRH_2b sites.

Corynanthine: a non-subtype selective α₁-adrenoceptor antagonist (at α_1A, α_1B and α_1D sites) and one of two diastereoisomers of yohimbine (the other being rauwolscine). Corynanthine can be isolated from bark of Corynanthe pachyceras.

Cotransmission: the release of more than one transmitter substance or modulator from nerve terminals following arrival of an action potential. Examples of cotransmission include the release of noradrenaline with ATP in postganglionic sympathetic neurones such as in blood vessels and the vas deferens.
Lundberg JM. Pharmacology of co-transmission in the autonomic nervous system: integrative aspects of amines, neuropeptides, adenosine triphosphate, amino acids and nitric oxide. Pharmacol Rev (1986) 48; 114-192

Coumarins: a class or oral anticoagulants which act by competitively inhibiting vitamin K in the biosynthesis of prothrombin.

Counter-irritants: also known as a rubifacients.

COX: cyclooxygenase

Coxibs: common name for cyclooxygenase inhibitors. Examples include celecoxib, rofecoxib, lumiracoxid, valdecoxib and etoricoxib.

CP-99,994: a selective NK1 tachykinin receptor antagonists.

CPNS: central and peripheral nervous systems.

CPP: conditioned place preference.

CRACC: calcium-release dependent calcium channels

Crack: also known cocaine or crack cocaine, the free base of cocaine and a recreational drug, probably used so for hundreds maybe thousands of years.

Crl:CD BR (CD) rat: an animal showing a low spontaneous incidence of Leydig cell adenoma.

CRO: contract research organization

Cromakalim: a potassium channel opener and a potent vasorelaxant. It acts by activating K(ATP) channels causing hyperpolarization of cell membranes which causes a decrease in cell excitability.

Cromoglicate: also known as sodium cromoglicate and more commonly spelled cromoglycate, an anti-allergy drug used clinically in the prophylaxis of asthma and to treat food allergy, allergic conjunctivitis and allergic rhinitis. Cromoglycate was the first non-steroidal drug that inhibited chemical mediator release at the cellular level to be used to treat asthma. It acts by stabilizing mast cell membranes so inhibiting the release of histamine and other mediators of inflammation.

Cross-over experiment or trial: a form of experiment or trial in which each subject or animal receives the test compound at least once and every test compound is administered to every subject or animal. Thus the treatments are crossed over to permit the effects of all test drugs to be studied in every subject thus allowing data for each preparation equally affected by the characteristics of each subject.

Crotalid venoms: hemorrhagic venoms from snakes of the genus Crotalus which include the western diamondback rattlesnake (Crotalus atrox).

Croton oil: a chemical carcinogenesis-promoting agent used to induce skin tumours in experimental animals.

Crotoxin (CTX): a potent neurotoxin from Crotalus durissus terrificus snake venom composed of two subunits: an acidic protein without catalytic activity and a basic phospholipase A₂. Crotoxin can block the depolarization caused by cholinergic agonists and can block neuromuscular transmission. It acts presynaptically by blocking neurotransmitter release but can also act postsynaptically by stabilizing the acetylcholine receptor in an inactive state. Crotoxin is used as a pharmacological tool to study neuronal and neuromuscular transmission.

Cruel poison: a poison which caused suffering for the animal which it is intended to kill. Squill was once use as a rat poison because rats lack a vomiting reflex and succumb to the central convulsant actions of the components of squill. Its use was outlawed long ago in many countries.

Cryptophycin: a compound which inhibits microtubule assembly by binding to the vinblastine sites on tubulin and exhibit broad antitumour activity at concentrations below those of taxol showing equal effects.

Crystal violet: a dye use in the determination of antitumour actions and tumor cell invasion inhibiting actions of drugs.

CSAIDs: cytokine suppressing anti-inflammatory drugs, drugs which exert anti-inflammatory effects by inhibiting the expression of pro-inflammatory cytokines. They bind to p38 mitogen-activated protein kinase (MAPK) thereby preventing its function and inhibiting the production of cytokines at the translational level. Examples include SKF 86002 which decreases the production of IL-1β from endotoxin-stimulated human macrophages and SB203580 which prevents IL-1β-induced PGE₂ release.

CSV: cat saphenous vein

Curare: also known as tube, ampi, pot and calabash, an arrow poison used by South American Indians in the Amazon and Orinoco valleys comprising a mixture of alkaloids from the roots and stems of the velvetleaf or ice vine (Chondrodendron tomentosum). The most important active component, d-tubocurarine, was isolated in 1935 and a standard curare preparation was used therapeutically in the 1940s to induce muscle relaxation during surgery. Curare acts by blocking the effects of ACh at nicotinic receptors (it is a nicotinic antagonist) which are found in ganglia and neuromuscular junctions.

Curareform: also known and curarimimetic, having curare-like actions, ie nicotinic receptor antagonism.

Cucurbitacins: tetracyclic triterpenes found in the form of glycosides in plants of the genus Cucurbitaceae and Cruciferae. These compounds have laxative effects and some have anticancer actions and pesticidal actions (because they have insect steroid hormone antagonist actions).

Cyanogenic: capable of producing cyanide ions in situ.

Cyclin-dependent kinases (cdk): a class of 8 enzymes (cdk 1 to cdk 8) which catalyze the transfer of the terminal phosphate group of ATP to the hydroxyl group of a tyrosine, threonine or serine residue in an acceptor molecule. Phosphorylation of one or more amino acids in an acceptor molecule can markedly change the function of acceptor molecules (ie phosphorylation is a biological switching mechanism) and in the cdks regulate many aspects of cell biochemistry including growth, movement, metabolism, cell differentiation and cell division.

Cyclin-dependent kinase inhibitors: compounds which inhibit cyclin-dependent kinases and thus inhibit the cell cycle. They are being developed mainly as anticancer treatments.
Hardcastle et al. Ann Rev Pharmacol Toxicol (2002) 42; 325-348

Cyclizine: an antihistamine and inhibitor of H₁ histamine receptors. It has anti-emetic actions and is used clinically to treat motion sickness, nausea, vomiting, vertigo and labyrinthine disorders.

Cyclocholine: a choline uptake inhibitor which acts by alkylating the choline carrier thus functioning as a neurotransmitter release modifier. It is a neurotoxin and has been used as a pharmacological tool.

Cyclooxygenases (COX): a family of cyclic endoperoxide isozymes which convert arachidonic acid to prostaglandins. COX-1, COX-2 and COX3 are known.

- COX-1 occurs constitutively and is responsible for the production of prostaglandins

- COX-2 is expressed de novo (it is induced) predominantly in inflammatory cells and inflamed tissues and is involved in the production of prostanoids. Both COX-1 and COX-2 are rate-limiting enzymes in the production of prostaglandins and prostanoids.

COX-3 is abundant in the cerebral cortex and heart and may mediate pain and fever although the amino acid sequence of COX-3 is unlike those of COX-1 and COX-2 so its function is humans is still unclear.

Cyclooxygenase inhibitor: inhibitors of cyclooxygenases which have anti-inflammatory, antipyretic and analgesic actions and which are used clinically to treat inflammation, arthritis, pain and fever. Examples include aspirin, paracetamol, indomethacin and diclofenac. Most COX inhibitors are nonspecific and inhibit COX 1 and COX 2 equally. Specific COX 2 inhibitors such as celecoxib and rofecoxid (now withdrawn from clinical use in the US) have been developed for the treatment of rheumatoid arthritis and osteoarthritis. Selective COX 1 inhibitors have been shown to reduce inflammation but they may also decrease the natural protective mucus lining of the stomach leading to erosion and gastrointestinal disorders.

N6-Cyclopentyladenosine: a selective A₁ adenosine receptor agonist.

8-Cyclopentyltheophylline: a selective A₁ adenosine receptor antagonist.

Cyclophosphamide: also known as cyclophospham, a cytotoxic, antineoplastic alkylating compound and nitrogen mustard (2H-1,3,2-oxaphosphorin-2-amine-N,N-bis(2-chloroethyl)-tetrahydro-1,2-oxide monohydrate) used in the treatment of cancer.

 In vivo it is metabolically activated in the liver by P₄₅₀ mixed function oxidases from its inactive form to a phosphoramide mustard which is a bifunctional alkylating agent. This alkylates the SH and NH₂ groups in proteins and the N⁷ of guanine in nucleic acids. Cyclophosphamide is also a carcinogen, teratogen and immunosuppressant the adverse effects of which are nausea, vomiting, bone marrow suppression, alopecia, cardiotoxicity and hemorrhagic cystitis (a disorder caused by acrolein, a metabolite of cyclophosphamide). Clinical applications include chronic lymphocytic leukaemia, lymphomas and solid tumours. It causes long-term suppression of antibody synthesis. It is also on of the most commonly used alkylating agents in cats and dogs and is used to treat lymphoreticular neoplasia, carcinomas, sarcomas, multiple myelomas and mast cell tumours.

Cyclopenta[a]phenanthrene: also known as a gonan or steran when fully hydrogenated, a chemical structure found in all steroids.

Cyclopiazonic acid: a specific inhibitor of endoplasmic reticulum Ca²⁺-ATPase and a mycotoxin (ie a fungal toxin) produced by Penicillium cyclopium. It has been used as a tool to elucidate the role of calcium ions in cellular processes.

Cycloplegics: drugs which paralyze the ciliary muscles of the eye making it impossible to focus on near objects. Mydriatic cycloplegic drugs exert their effects by blockade of innervation to the sphincter pupillae and ciliary muscles (ie they have muscarinic antagonist actions) and include atropine, cyclopentolate, homatropine and tropicamide.

Cyclosporin: ciclosporin.

Cyclothialidines: a class of gyrase B inhibitors with antibiotic and anticancer activity .They can be isolated from Streptomyces filipinensis and are potent inhibitors of the supercoiling activity of DNA gyrase and inhibit the ATPase activity of the B subunit.

Cynomolgous monkey: the crab-eating macaque (Macaca fascicularis) and a member of the macaque family of monkeys.

Cypionate: a cyclopentane propionate salt. Examples include testosterone cypionate.

Cyproterone: an anti-androgen used clinically to treat prostate cancer and sexual deviation in males in the form of its acetate salt.

Cystatins: a family of about 12 proteins present in mammals, birds, fish, insects, plants and some protozoa and potent peptidase inhibitors. Type 1 cystatins (A and B) are mainly intracellular, type 2 cystatins (C, D, E/M, F, G, S, SN and SA) are extracellular and type 3 cystatins (L- and H-kininogens) are intravascular proteins. They inhibit calpain and are important in pathology as they function in intracellular protein degradation (cathepsins B, H and L) and in the remodelling of bone (cathepsin K).
Abrahamson M, Alvarez-Fernandez M, Nathanson CM. Cystatins. Biochem Soc Symp. (2003) 70; 179-99

CysLT: cysteinyl leukotriene, a type of leukotriene.

Cystine stone-forming dogs: an animal models for cystinuria comprising dogs of a variety of breeds such as dalmatian and corgis which develop kidney stones. They have been used to test the effects of drugs used to treat renal calculi.

Cytarabine: also known as ARA-C and cytosine arabinoside, an antimetabolite (it is an analogue of the naturally occurring 2’-deoxycytidine) and inhibitor of pyrimidine synthesis used clinically in the induction of remission of acute myeloblastic leukaemia. It enters cells and is then converted by the same phosphorylation reaction as physiological nucleosides into the active nucleotide triphosphate ARA-CTP which then inhibits the binding of deoxycytidine triphosphate to DNA polymerase thereby inhibiting DNA synthesis. Cytarabine is also effective in the control of viral infections.

Cytochalasins: a group of cytostatic fungal metabolites (cytochalasins A, B, C, D, E, F, G and H) obtained from Helminthosporium dematioideum, Metarrhizium anisopliae and Rosellina necatrix. They are potent inhibitors of actin polymerization and inhibit contractile actin microfilament formation by binding to the fast-growing ends of actin filaments. They also arrest the cell cycle at G1-S transition.

Cytokines: a group of intercellular regulatory polypeptides and glycoproteins which function in intercellular signaling usually via binding to specific cell surface receptors. Cytokines activate and deactivate phagocytes and immune defense cells, they increase and decrease the functions of immune defense cells and promote and inhibit a variety of innate body defenses. Examples include bone morphogenic proteins, interleukins, tumor necrosis factor and interferons. They mediate a broad range of inflammatory and connective tissue diseases and are targets for the development of drugs to treat inflammation, tissue degeneration and arthritis amongst others. They can be classified a number of ways but a simple classification is:
- Haematopoietic cytokines - control bone marrow cell proliferation and differentiation and include IL-3, IL-7, IL-11, GM-CSF and G-CSF,
- Regulatory cytokines act primarily on lymphocytes and include IL-2, IL-4, IL-5, Il-9, IL-10, IL-12, IL-13, IFN-γ and TGF-β,
- Pro-inflammatory cytokines which promote, prolong and amplify inflammatory responses. Examples include IL-1, IL-6, TNF-α and IL-8.

See http://www.copewithcytokines.de/cope.cgi and http://cmbi.bjmu.edu.cn/cmbidata/cgf/CGF_Database/cytweb/

Cytokine receptors: cell surface receptors sensitive to  cytokines. They are broadly classified into four major types of receptor: 1) haematopoietic family receptors are dimers of trimers with cysteine residues conserved in their extracellular domains and conserved Trp-Ser-X-Trp-Ser sequences and mediate the actions of Il-2, Il-3 Il-4, IL-5, Il-6, IL-7 and GM-CSF, 2) interferon family receptors comprises four extracellular domains and include receptors for IFNα, IFNβ and IFNγ, 3) tumor necrosis factor receptor family comprise four extracellular domains and include receptors for TNFα, TNFβ, membrane-bound CD40 and Fas, and 4) chemokine family receptors are G protein-coupled 7 transmembrane helices and examples include receptors for IL-8, MIP-1, RANTES, CCR5 and CXCR4.

Cytokine receptor antagonists: compounds which bind to cytokines or their receptors to inhibit their actions. They can be endogenous substances or synthetic compounds are being developed to treat a broad range of immune diseases, allergies and inflammation.

Cytokine synthesis inhibitors: compounds which inhibit the biosynthesis of cytokines. They are being developed for the treatment of inflammatory disorders, autoimmune disease and microbial infections because inhibition of cytokine production inhibits communication between immune effector cells. Examples include tumour necrosis factor-a and interleukin synthesis inhibitors.

Cytoprotection: a process in which chemical compounds protect cells from harmful agents.

Cytostatic: a compound which halts cell differentiation and division. When this compound is removed cell division resumes in contrast to a cytotoxic compound which kills the cells.

Cytotoxic: a compound which kills cells. They are generally of use in the treatment of cancer but predictably have side effect relating to the killing on healthy and rapidly growing cells such as myelosuppression (including leukopaenia and thrombocytopaenia) gastrointestinal upset and anaemia.

Cysteine proteases: a class of protein-digesting enzymes which include papain, cathepsins, caspases and calpains.