Improved Non-steroid Anti-inflammatory Drugs: Cox-2 Enzyme Inhibitors by Sir John R. VaneImproved Non-steroid Anti-inflammatory Drugs: Cox-2 Enzyme Inhibitors by Sir John R. Vane

Improved Non-steroid Anti-inflammatory Drugs: Cox-2 Enzyme Inhibitors

bySir John R. VaneEditorJack H. Botting, R.M. Botting

Paperback | December 25, 2011

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In 1971, Vane proposed that the mechanism of action of the aspirin-like drugs was through their inhibition of prostaglandin biosynthesis. Since then, there has been intense interest in the interaction between this diverse group of inhibitors and the enzyme known as cyclooxygenase (COX). It exists in two isoforms, COX-l and COX-2 (discovered some 5 years ago). Over the last two decades several new drugs have reached the market based on COX-l enzyme screens. Elucidation of the three-dimensional structure of COX-l has provided a new understanding for the actions of COX inhibitors. The constitutive isoform of COX, COX-l has clear physiological functions. Its activation leads, for instance, to the production of prostacyclin which when released by the endothelium is anti-thrombogenic and anti-atherosclerotic, and in the gastric mucosa is cyto­ protective. COX-l also generates prostaglandins in the kidney, where they help to maintain blood flow and promote natriuresis. The inducible isoform, COX-2, was discovered through its activity being increased in a number of cells by pro­ inflammatory stimuli. A year or so later, COX-2 was identified as a distinct isoform encoded by a different gene from COX-I. COX-2 is induced by inflammatory stimuli and by cytokines in migratory and other cells. Thus the anti-inflammatory actions of non-steroid anti-inflammatory drugs (NSAIDs) may be due to the inhibition of COX-2, whereas the unwanted side-effects such as irritation of the stomach lining and toxic effects on the kidney are due to inhibition of the constitutive enzyme, COX-I.
Sir John Vaneis the Director General at the William Harvey Research Institute, an independent charitable foundation within Queen Mary and Westfield College of the University of London, UK.Sir John Vane shared the Nobel Prize in Physiology or Medicine in 1982 for his discoveries of the mechanism of action of aspirin and of prostacyclin,...
Title:Improved Non-steroid Anti-inflammatory Drugs: Cox-2 Enzyme InhibitorsFormat:PaperbackDimensions:200 pages, 23.5 × 15.5 × 0.01 inPublished:December 25, 2011Publisher:Springer-Verlag/Sci-Tech/TradeLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:9401090319

ISBN - 13:9789401090315

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Table of Contents

Preface. 1. Overview - Mechanisms of Action of Anti-Inflammatory Drugs; J. Vane, R. Botting. 2. The Three-Dimensional Structure of Cyclooxygenases; R.M. Garavito. 3. The Dilemma of Two Cyclooxygenases: Identifying the Roles of COX-1 and COX-2 in Inflammation and Apoptosis; D. Simmons, et al. 4. Inducible Enzymes with Special Reference to COX-2 in the Inflammatory Response; D. Willoughby, et al. 5. NSAID Mechanism of Action: The Role of Intracellular Pharmacokinetics; L. Herbette, et al. 6. Differential Inhibition of COX-1 and COX-2 in vitro and Pharmacological Profile in vivo of NSAIDs; M. Pairet, G. Engelhardt. 7. COX-2 Expression and Inhibition in Human Monocytes; C. Patrono, et al. 8. Expression and Regulation of COX-2 in Synovial Tissues of Arthritic Patients; L. Crofford. 9. An Inhibitor of Injury-Induced COX-2 Transcriptional Activation Elicits Neuroprotection in a Brain Damage Model; N. Bazan, G. Allan. 10. COX-2 Expression in Labour; P. Bennett, D. Slater. 11. Re-Evaluation of Gut Toxicity of NSAIDs; D.N. Bateman. 12. NSAID: Can Renal Side Effects be Avoided? J. Frölich, D. Stichtenoth. 13. Pharmacology, Safety Data and Therapeutics of COX-2 Inhibitors; P. Emery. Index.