By J. R. Vane, R. M. Botting (auth.), Sir John Vane, Dr Jack Botting, Dr Regina Botting (eds.)
ISBN-10: 9401090297
ISBN-13: 9789401090292
ISBN-10: 9401090319
ISBN-13: 9789401090315
In 1971, Vane proposed that the mechanism of motion of the aspirin-like medicines was once via their inhibition of prostaglandin biosynthesis. seeing that then, there was excessive curiosity within the interplay among this assorted team of inhibitors and the enzyme referred to as cyclooxygenase (COX). It exists in isoforms, COX-l and COX-2 (discovered a few five years ago). during the last twenty years numerous new medications have reached the marketplace in keeping with COX-l enzyme monitors. Elucidation of the 3-dimensional constitution of COX-l has supplied a brand new realizing for the activities of COX inhibitors. The constitutive isoform of COX, COX-l has transparent physiological capabilities. Its activation leads, for example, to the creation of prostacyclin which while published via the endothelium is anti-thrombogenic and anti-atherosclerotic, and within the gastric mucosa is cyto protecting. COX-l additionally generates prostaglandins within the kidney, the place they assist to take care of blood movement and advertise natriuresis. The inducible isoform, COX-2, used to be found via its job being elevated in a couple of cells by means of seasoned inflammatory stimuli. A yr or so later, COX-2 used to be pointed out as a unique isoform encoded through a distinct gene from COX-I. COX-2 is brought on by means of inflammatory stimuli and by means of cytokines in migratory and different cells. hence the anti inflammatory activities of non-steroid anti inflammatory medicinal drugs (NSAIDs) could be end result of the inhibition of COX-2, while the undesirable side-effects similar to inflammation of the tummy lining and poisonous results at the kidney are because of inhibition of the constitutive enzyme, COX-I.
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Extra info for Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors
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Xie W, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogenresponsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA. 1991;88:2692-6. 23. Simmons DL, Levy DB, Yannoni Y, Erikson RL. Identification of a phorbol ester-repressible v-src inducible gene. Proc Nat! Acad Sci USA. 1989;86: 1178-82. 24. Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR. TIS 10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase!
57. Whittle BJR, Higgs GA, Eakins KE, Moncada S, Vane JR. Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa. Nature. 1980;284:271-3. 58. Vargaftig BB. Salicylic acid fails to inhibit generation of thromboxane A, activity in platelets after in vivo administration to the rat. J Pharm Pharmacol. 1978;30: 101-4. 59. Flower RJ, Vane JR. Inhibition of prostaglandin synthetase in brain explains the antipyretic activity of paracetamol (4-acetamidophenol). Nature.
48. Miller TA. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. Am J Physiol. 1983;245:G601-23. 49. Robert A, Hanchar AJ, Lancaster C, Nezamis JE. Prostacyclin inhibits enteropooling and diarrhea. In: Vane JR, Bergstrom S, editors. Prostacyclin. New York: Raven Press; 1979: 147 - 58. SO. Higgs GA, Vane JR, Hart FD, Wojtulewski JA. Effects of anti-inflammatory drugs on prostaglandins in rheumatoid arthritis. In: Robinson HJ, Vane JR, editors.
Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors by J. R. Vane, R. M. Botting (auth.), Sir John Vane, Dr Jack Botting, Dr Regina Botting (eds.)
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