Facilitated diffusion: diffusion of a substance across a membrane by attachment to a carrier such as a macromolecule but which is not an energy-dependent mechanism. In this process the substance moves down a concentration gradient at a faster rate than with simple diffusion alone and exhibits Michaelis-Menten saturation kinetics, is relatively substrate specific and exhibits competitive inhibition kinetics. Facilitated diffusion is not a major mechanism of drug transport but is important for the reabsorption of glucose in the kidney and for the intestinal absorption of vitamin B₁₂.

Factor Xa: a serine protease which activates prothrombin (a 70kDa protein synthesized in the liver) to form thrombin which converts fibrinogen to fibrin which in turn forms a mesh-like blood clot. Factor Xa actually exists in blood as a proenzyme (Factor X) which is activated by either Factor VIIa or Factor IXa. Thus, when Factor X is activated to form Factor Xa blood coagulation is propagated.

Factor Xa inhibitor: inhibitors of Factor Xa and compounds used to inhibit blood coagulation and are thought to provide better safety and efficacy than many of the currently available anticoagulants. Examples of Factor Xa inhibitors include BAY-59-7939 and YM-150 which are being developed for the treatment of thrombosis.

Factorial design: a form of clinical trial in which several treatments are investigated at the same time. Although it is assume that such as trial could answer several questions at the same time, patient numbers tend to be higher than for parallel group trials and factorial trials are considered appropriate when any interaction between the drugs being investigated is of primary concern.

Facultative: relating to the ability of organisms, usually bacteria, to adapt an alternative lifestyle to the one it is usually accustomed. A facultative anaerobe, for example, is an organism which usually grows anaerobically but which, in the right environment, can grow aerobically. The opposite is obligate which refers to an organism which can only grow in a specific environment and cannot adapt.

Fade: the lessening of a response in the continued presence of an agonist. A term often confused with desensitization and tachyphylaxis.

False precursor: a compound structurally resembling a natural precursor of a neurotransmitter and a compound which can take its place in the biochemical synthesis of the natural neurotransmitter. This false precursor is metabolised to form a compound which is not the neurotransmitter and so lacks its effects. Examples include the false cholinergic precursor N-amino-N,N-dimethylaminoethanol which is metabolised to form acetyl-NADe. This causes replacement of endogenous acetylcholine. Another example is the cyclic choline analogue, 3-hydroxy-N,N-dimethylpiperidinium. False precursors often lead to the formation of false transmitters.

False transmitter: a substance which resembles a natural transmitter, which is stored and released by neurones but which differs from natural transmitters in that their postsynaptic actions are much weaker and often cause impairment of signal transmission. An example is a-methylnoradrenaline. If methyldopa, the a-methyl analogue of dopa, is administered to animals it is metabolised by dopa decarboxylase to form a-methyldopamine and then by dopamine-β-hydroxylase to form aa-methylnoradrenaline. This is then taken up and stored in vesicles in adrenergic neurones, but when released has only a fraction of the potency of noradrenaline.

Famotidine: a histamine H₂ receptor blocker used clinically for the treatment of gastric and duodenal ulcers and Zollinger-Ellison syndrome. It decreases gastric acid secretion.

Farnesyltransferase (FTP, FTase): an enzyme (EC 2.5.1.58) officially known as protein farnesyltransferase and one of a family of enzymes  which catalyzes the transfer of a farnesyl group to the Ras protein. Farnesylation occurs on the cysteine residue at the COOH terminal of Ras proteins and this critical modification renders the protein oncogenic. After farnesylation and other modifications, the Ras protein embeds itself in the cell's plasma membrane where it becomes involved in the signal transduction pathways which control growth and differentiation of the cell.

Farnesyl-protein transferase inhibitors (FTI): inhibitors of protein farnesyltransferase which can be classified into mainly two different types of inhibitors, farnesyl diphosphate competitors and CAAX peptidomimetics.
Farnesyl diphosphate competitors act by inhibiting farnesyl transferase by competing with one of its substrates, farnesyl diphosphate, whereas CAAX peptidomimetics mimic the other substrate, the C-terminal CAAX motif of Ras protein. FTIs are being developed as anticancer drugs. Examples include lonafarnib, R115777 and BMS-214662.
Kelloff GJ et al. Farnesyl protein transferase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev (1997) 6; 267-282
Johnston SR. Farnesyl transferase inhibitors: a novel targeted therapy for cancer. Lancet Oncol (2001) 2(1);18-26

Farnesyl transferase: also known as squalene synthase and officially as farnesyl-diphosphate farnesyl transferase, an enzyme (EC 2.5.1.21) which converts presqualene diphosphate to squalene. Squalene is an important intermediate in the hepatic synthesis of cholesterol. Farnesyl transferase in tightly bound to endoplasmic reticular membranes and is a key enzyme in the biosynthesis of cholesterol. This enzyme is often confused with protein farnesyltransferase.

Farnesyl transferase inhibitors: compounds which inhibit the hepatic enzyme farnesyl transferase and decrease the synthesis of cholesterol. These inhibitors are being developed for potential use in the treatment of arteriosclerosis and other vascular disorders related to hypercholesterolemia.

Fast receptors: also known as inotropic receptors, ligand-gated receptors present in the mammalian brain and other tissues.

Fatty acid amide hydrolase (FAAH): a membrane-bound enzyme which hydrolyses of a number of primary and secondary fatty acid amides including the neuromodulatory compounds anandamide and 2-arachidonoylglycerol and the sleep-inducing substance oleamide. It inactivated these compounds by degrading them to arachidonic acid.

Fatty acid amide hydrolase inhibitors: compounds which inhibit fatty acid amide hydrolase and so potentiate the effects of endocannabinoids by preventing their degradation. These inhibitors can prolong the endogenous antinociceptive effects of endocannabinoids and so FAAH inhibitors are being developed for the treatment of pain, anxiety and insomnia. Examples of FAAH inhibitors include malhamensilipin A, grenadadiene and arachidonylserotonin.

Fear-potentiated startle:an animal model of fear. An auditory startle response can be potentiated by coadministering the startle-eliciting noise with a stimulus that has previously been assocoated with an electric shock to potentiate the fear. Anxiolytics such as benzodiazepines decrease or block the this startle response.

Febrifuge: also referred to as an antipyretic, a drug which lowers body temperature to combat fever.

Fenamic acids: also known as N-arylanthranilic acids and anthranilates, a class of NSAIDs developed as nitrogen isosteres of salicylic acid. They include mefanamic acid, flufenamic acid and meclofenamic acid and are cyclooxygenase inhibitors. The fenamic acid moiety is shown in blue below.



Fenfluramine: a centrally acting appetite suppressant which has been used in the treatment of weight loss but has serious side effects of valvular heart disease and pulmonary hypertension. It appears to cause the release of endogenous 5-HT which acts mainly on postsynaptic 5-HT_2A receptors.

Fenoldopam: a D₁-like dopamine receptor agonist used in the treatment of hypertensive emergency as it decreases blood pressure.

Fentanyl: a synthetic opioid analgesic used clinically for the treatment of breakthrough pain in patients receiving opioid therapy for chronic pain and for chronic intractable pain. It is used in veterinary pharmacology as part of a anaesthetic induction regimen in dogs and in the form of a continuous infusion as an analgesic. Fentanyl is a μ-opioid receptor agonist with about 80 times the potency of morphine.

Ferret: a small mammal which is often used to test the effects of anti-emetic drugs.

Fibrates: also known as fibric acids, fibric acid derivatives used to reduce circulating levels of VLDL by decreasing its synthesis and secretion. They include clofibrate, gemfibrozil, benzafibrate, etofibrate, etophyllinclofibrate and ciprofibrate. Fibrates are used clinically in the treatment of hyperlipidemia and in the prevention of coronary heart disease often in patients who have not responded to diet therapy. They appear to act by stimulating lipoprotein lipase and so increase the hydrolysis of triglyceride in chylomicrons and VLDL particles. They may also decrease liver VLDL production and increase the uptake of VLDL by the liver.

Fibrosis: also known as scarring, a process of collagen deposition in a tissue of organ which follows proliferation of fibroblasts. Fibrosis is a normal tissue repair response to chronic or acute injury.

Fibronectin: a general cell adhesion molecule which is involved in tissue repair, embryogenesis, blood clotting and cell migration and adhesion. It exists in two main forms, ie as an insoluble glycoprotein dimer in the extracellular matrix and as a soluble disulphide-linked dimer found in the plasma. The plasma form is synthesized by hepatocytes and the extracellular form is made by fibroblasts, chondrocytes, endothelial cells, macrophages and by some types of epithelial cells.

Fiducucial limits: also known as confidence limits.

Finasteride: a synthetic 4-azasteroid compound and a competitive and specific inhibitor of steroid type II 5-reductase which catalyses the formation of 5-dihydrotestosterone from testosterone. Finasteride is used clinically to treat symptomatic and benign prostate hyperplasia.

Finkleman preparation: an in vitro preparation of rabbit ileum with attached mesenteric nerves used to investigate the role of postganglionic sympathetic nerves in isolated intestines. Finkleman attempted to compare the effects of nerve stimulation with those of adrenaline as at the time of his experiments little was known about sympathetic innervation of the gut and the sympathetic neurotransmitter was thought to be adrenaline. He showed that nerve stimulation caused the release of an inhibitory substance but did not conclusively show that adrenaline was not the neurotransmitter involved. In fact, it was not until about 1960 that the identity of this transmitter was determined. The Finkleman preparation involves two ileal segments set up in such a way that the Ringer's solution flowing over one also flows over the other. The upper segment is isolated with the mesenteric nerve intact.
Finkleman B. On the nature of inhibition in the intestine. J Physiol (London) (1930) 70;145

First-dose effect: an effect of a drug where its pharmacological actions are manifested suddenly after the first dose is taken. An example is a rapid decrease in blood pressure after an ACE inhibitor is taken and first dose effects are often associated with hypotensive drugs. During the first dose effect, the patient's blood pressure drops rapidly causing dizziness, nausea and possibly fainting. These symptoms are more pronounced after the first dose than after subsequent doses as the tissues are naive and sensitive to the effects of the drug. By the time subsequent doses are given, the tissues may have become less sensitive to the drug.

First-line therapy: the drugs which are preferred to be used in the initial treatment of a disease.

First messenger: a term used to describe a compound, molecule or ion which conveys a signal to a cell from extracellular sites. Examples include neurotransmitters such as acetylcholine and serotonin, ions such as calcium (which also functions as a second messenger) and hormones such as insulin.

First order kinetics: also known as linear kinetics, a term used in enzyme kinetic and pharmacokinetics to describe a reaction which proceeds at a rate which is proportional to the concentration of substrates participating in the reaction. First order kinetics is used to describe drug absorption from its site of administration and drug metabolism and elimination from the body.

First-pass effect: metabolism of drugs which have been given orally by the gut wall and/or the liver which reduce the amount of the drug getting into the blood. For some drugs such as the analgesic meptazinol the first-pass effect is marked as the glucuronide conjugate is synthesized in the liver.

Fischer 344 rat (F344): an inbred strain of rat which has a high spontaneous incidence of Leydig cell adenomas.

Fischer rats: derived originally from a colony used in 1920 at the Colombia Institute for Cancer Research, Fischer rats are an extremely dependable strain of inbred rats commonly used in studies requiring homogenous populations. Their slow growth rate means that they are preferred for long-term studies.

Fisher's exact test: a statistical method devised by the British geneticist and biostatistician R.A. Fisher (1890-1962) which can be used to compare data in a two by two contingency table, eg when a new therapy is compared to a standard therapy or control group and where the outcome is measure in binary form such as live or dead, diseased or healthy, cured or not cured and infected or uninfected. This test only provides a p-value and does not produce a confidence interval but can be used on small sample sizes. Fisher's exact test is often used as an alternative to the Chi-square test.

Flecainide: a Class Ic antiarrhythmic drug with local anaesthetic actions used clinically to treat AV nodal reciprocating tachycardia and arrhythmias associated with Wolff-Parkinson-White syndrome. It markedly reduces cardiac conduction velocity without changing action potential duration and may depress sinus node automaticity.

Fleming, Sir Alexander (1881 - 1955): British physician and microbiologist who shared the 1945 Nobel Prize for Physiology or Medicine with Florey and Chain for "for the discovery of penicillin and its curative effect in various infectious diseases".
http://nobelprize.org/medicine/laureates/1945/fleming-bio.html

Flinders sensitive line (FSL) rat: a rat model of depression and selectively bred for its increased responses to the anticholinesterase DFP. It was originally proposed as an animal model of depression because it is supersensitive to the behavioral and hormonal effects of muscarinic agonists. This line of rats was established at Flinders University in Australia by selectively breeding rats for differential responses to anticholinesterase agent using outbred Sprague-Dawley rats.
Overstreet DH. The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Biobehav Rev (1993) 17(1);51-68

Florey, Lord Howard Walter (1898-1968): also known as Baron Florey of Adelaide and Marston, Australian-born physician and physiologist who shared the 1945 Nobel Prize for Physiology or Medicine with Fleming and Chain 'for the discovery of penicillin and its curative effect in various infectious diseases'.
http://nobelprize.org/medicine/laureates/1945/florey-bio.html

Fluoropyrimidines: a class of anticancer compounds which include 5-fluorouracil, 5'-deoxy-5-fluorouridine and torafur.

Fluoroquinolones: a class of bactericidal drugs used clinically against both gram-positive and gram-negative bacteria. Examples include enrofloxacin, norfloxacin and ciprofloxacin. They act by inhibiting bacterial DNA gyrase so inhibiting bacterial replication. The fluoroquinolone moiety is shown in blue.



5-Fluorouracil: a synthetic fluorinated pyrimidine anticancer compound first synthesised in 1957 which inhibits 2'-deoxythymidylate synthesis by inhibiting thymidylate synthase and so inhibits DNA production. It stops the growth of proliferating cells and has been used in the treatment of cancer and viral infections.
5-FU is actually a prodrug which requires intracellular modification be become active. It is converted to 5-FUDR (2 deoxy-5-fluorouridine) by thymidine phosphorylase and 5-FUDR is then phosphorylated by thymidine kinase to form 5-FdUMP. Then in the presence of methylene tetrahydrofolate 5-FdUMP forms a stable ternary complex with thymidylate kinase and inhibits its actions.

Fly agaric toxins: toxins from the fly agaric mushroom Amanita muscaria. These toxins include muscarin, muscaridin, ibotenic acid, muscimol and muscazone. Both ibotenic acid and muscimol inhibit motor functions although poisoning is not usually fatal. Extracts from the fly agaric mushroom have hallucinogenic properties as they contain the psychotropic muscimol.

Flucloxacillin: a penicillin antibacterial which is not inactivated by penicillinases and so is used clinically to treat β-lactamase-producing staphylococci infections, pneumonia, impetigo, osteomyelitis and staphylococcal endocarditis. Flucloxacillin is acid-stable and can be given orally.

Fluconazole: an azole antifungal compound used clinically to treat mucosal candidiasis, tinea pedis, invasive candidal infections such deep and disseminated candidiasis and for the prevention of fungal infections in immunocompromised patients and to prevent relapse of cryptococcal meningitis as fluconazole penetrates into the cerebrospinal fluid.

Flucytosine: also known as 5-fluorocytosine, 5-FC and 4-amino-5-fluoro-2-pyrimidone, an antimetabolite and antifungal used clinically to treat Candida and Cryptococcus infections. It inhibits fungal protein synthesis by replacing uracil with 5-flurouracil in fungal RNA and also inhibits thymidylate synthetase via 5-fluorodeoxy-uridine monophosphate so inhibiting the actions of fungal DNA.

p-Fluorohexahydrosiladefendol: a selective M₂ muscarinic cholinoceptor antagonist.

Fluoxetine: more popularly known as Prozac^®, a selective serotonin reuptake inhibitor (SSRI) used clinically in the treatment of depressive illness, bulimia nervosa, obsessive compulsive disorders and premenstrual dysphoric disorder.

Fluphenazine: a classical (also known as typical) antipsychotic compound used clinically to treat schizophrenia and other psychoses such as hallucinations, delusions and hostility. Fluphenazine block postsynaptic mesolimbic D1 and D2 dopamine receptors in the CNS. It is used as a decanoate salt which shows slower release from depot sites than the hydrochloride salt.

Fluvaxamine: a selective serotonin release inhibitor.

Foetotoxic (fetotoxic): toxic to fetuses, ie the period of life between the completion of organogenesis to birth.

Folate antagonists: a class of antimetabolites used in the treatment of cancer. They inhibit the conversion of folic acid to tetrahydrofolate by dihydrofolate reductase. Examples include methotrexate which is folic acid analogue.

Folic acid: also known as pteroylglutamic acid, a water-soluble pteridine derivative and vitamin necessary in the diets of mammals. Its active form is 5,6,7,8-tetrahydrofolic acid which is formed by the action of dihydrofolate reductase on dietary folic acid and is a coenzyme in the transfer of one carbon units. Folic acid is the parent compound of folates, a class of compound essential in DNA synthesis because they are cofactors in the cellular synthesis of purines and pyrimidines. Folic acid itself is used clinically in the treatment of folic acid-deficient megaloblastic anaemia and in the prophylaxis of chronic haemolytic disease.

Folic acid antagonist: folate antagonist

Folts model: a model of antiplatelet activity which may be useful in the study of mechanisms which enhance or inhibit arterial thrombosis in stenosed arteries with endothelial and medial injury. It has been used as an experimental model of unstable angina and is used in the evaluation of thrombolytic drugs.
Folts J. An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Circulation (1991) 83(6 Suppl):IV3-14.

Foot misplacement: a test to determine sensorimotor recovery following spinal or brain injury. A rat or mouse with spinal or brain injury is made to walk along a horizontal ladder towards a target it perceives as safe such as a dark box and the number of times it misplaces a paw, ie misses a rung, is taken as a measure of sensorimotor recovery with fewer misplacements taken as better recovery.

Footshock: an animal model of chronic mild stress in which an animal receives electric shocks to the foot over a period of time, for example, 20 minutes a day for 2 weeks. This stress caused changes in the animals behaviour such as intracranial self-stimulation (ICSS) and sucrose consumption and these changes can be monitored to determine the effects of drugs on them.

Forced diuresis: a method of altering urinary pH usually with the intention of eliminating a poison from the body. For example, intravenous administration of sodium bicarbonate will make the urine more basic and will facilitate the excretion of weakly acidic drugs such as salicylates.

Forced swimming test (FST): an animal model of depression in which an animal trpically a rat or mouse is forced to swim in a tank with no way out or no where to rest until the point of despair. This swimming time decreases as the animal is forced to swim on successive days as it demonstrates learned helplessness, ie it gives up trying to swim to safety but only makes those swimming movements necessary to stay obove the water. This model is used to test the effects of antidepressants which increase swimming actions.
Porsolt RD et al. Depression: a new animal model sensitive to antidepressant treatments (1977) Nature, Apr 21;266:730-2
Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol (1997) 8(6-7):523-32

Formalin test: a test for the analgesic actions of compounds in which diluted formalin solution (1 to 5%) is injected into the paw of a rat or mouse to induce discomfort and pain. The animal will normally respond by licking and biting the injected paw and the response to pain is delayed by analgesics. This method comprises two components of early pain and later inflammation.
Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain (1977) 4; 161-174

Formoterol: also known as eformoterol, a selective β₂-adrenoceptor agonist used clinically as its fumarate salt to treat reversible airways obstruction including nocturnal asthma, for the prevention of exercise-induced bronchospasm.

Formyl peptide receptors: a family of seven-transmembrane domain, G protein-coupled receptors which are important in host defense and inflammation. They are expressed by phagocytic leukocytes.
http://pharmrev.aspetjournals.org/cgi/content/abstract/61/2/119

Forskolin: a naturally occurring diterpene alkaloid obtainable from the plant  Coleus Forskohlii which directly stimulates adenylate cyclase. It is used extensively to increase cAMP levels and to elicit cAMP-dependent physiological responses.

Foscarnet: also known as phosphonoformate, a DNA polymerase inhibitor and antiviral. It is used clinically to treat cytomegalovirus retinitis in AIDS and mucocutaneous herpes simplex virus infections.

Foxglove: a plant (Digitalis purpurea) commonly found in Europe and the US from which digitalis is obtained.

FPTase: farnesyl-protein transferase.

FRAME: Fund for the Replacement of Animals in Medical Experiments, a UK organization whose long-term aim is to have animals used in experiments replaced by alternative methods.
http://www.frame.org.uk/

Fraser mouse: an animal model of hereditary cataracts in which there is altered expression of type I collagen.

Free radical: atoms or molecules with unpaired electrons. They are important in many physiological functions particularly in the immune system where they help phagocytic cells destroy bacteria. Cancers are thought to arise due to the damage free radicals inflict on DNA. The two main free radicals are superoxide and the hydroxy radical.
The body has endogenous mechanisms to reduce the damage these free radical scan do to it such as with the enzymes superoxide dismutase, catalase and glutathione peroxidase.

Free radical scavenger: a compound which can scavenge and eliminate free radicals.

Freund's adjuvant: an adjuvant comprising an oil-in-water emulsion of a detergent and a killed mycobacterium usually Mycobacterium tuberculosis (Freund's complete adjuvant) or no killed bacteria or bacterial components (Freund's incomplete adjuvant). It is used to enhance immune reactions to antigen and is thought to slow antigen clearance from the site of inoculation as well as causing an influx of leucocytes.

Frostbite injury: a form of cold injury.

Fructose-1,6-bisphosphatease (FBPase): a liver enzyme which participates in gluconeogenesis.

Fructose-1,6-bisphosphatase inhibitors: compounds which inhibit FBPase and so secrease liver gluconeogenesis. They are being developed for the treatment of diabetes. Examples include MB06322 (CS-917), a prodrug of  MB05032.

Frusemide: also more correctly known as furosemide, a high-ceiling diuretic first discovered in 1959. It is more a more potent diuretic than the thiazides and is used clinically to treat oedema and oligouria due to renal failure.

FSH: Follicle stimulating hormone.

Fumagillin: an inhibitor of endothelial cell proliferation and angiogenesis. It is produced by Aspergillus fumigatus and is used for the control of the microsporidian disease nosema (caused by Nosema apis) in honey bees. It also has anti-amoebic and general anti-protozoal function and was once used to treat malaria. Fumagillin can be applied topically to the conjunctiva in the treatment of microsporidial keratoconjunctivitis

Functional antagonism: a type of antagonism.

Funnel plot:  a graphical plot of sample size against effect size. It can be used to investigate publication bias for example.

Furchgott , Robert Francis (1916-): US biochemist and pharmacologist who identified endothelium-derived relaxing factor as nitric oxide in 1986 independently of Louis Ignarro and showed that is could function as a signaling molecule. He shared the 1988 Nobel Prize for Physiology or Medicine with Ignarro and Murad "for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system".
Furchgott RF. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide. JAMA (1996) 276;1186-8
http://www.nobel.se/medicine/laureates/1998/furchgott-autobio.html

Furchgott analysis: a method to measure the affinity of an agonist for a receptor. This method compares concentration-response curves before and after blockade of receptors with and irreversible antagonist.
Furchgott RF. Adv Drug Res (1966) 3; 21-55

Furchgott & Bursztyn method: a method to determine both the dissociation constant and relative efficiency of an agonist interacting with a receptor.
Furchgott RF and Bursztyn P. Comparison of dissociation constants and of relative efficacies of selected agonists acting on parasympathetic receptors. Ann NY Acad Sci (1967) 144; 882-898

Fusidic acid: a tetracyclic, triterpene narrow-spectrum antibacterial compound obtained from Fusidium coccinium. It is active against Staphylococcus, Clostridium, Neisserias, Corynebacterium and Mycobacterium tuberculosis. It is used clinically in osteomyelitis, staphylococcal endocarditis, staphylococcal eye infections and staphylococcal skin infections. It inhibits protein synthesis by inhibiting the interaction of the elongation factor EFG with the small ribosomal subunit.