Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors

Editors: Vane, Sir John R., Botting, Jack, Botting, R.M. (Eds.)

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About this book

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.

About the authors

Sir John Vane is 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, as well as his work on other prostanoids. Jack Botting is Consultant at the William Harvey Research Institute, an independent charitable foundation within Queen Mary and Westfield College of the University of London, UK.

Table of contents (13 chapters)

Table of contents (13 chapters)
  • Overview — mechanisms of action of anti-inflammatory drugs

    Pages 1-27

    Vane, J. R. (et al.)

  • The three-dimensional structure of cyclooxygenases

    Pages 29-43

    Garavito, R. M.

  • The dilemma of two cyclooxygenases: identifying the roles of COX-1 and COX-2 in inflammation and apoptosis

    Pages 45-65

    Simmons, D. L. (et al.)

  • Inducible enzymes with special reference to COX-2 in inflammation and apoptosis

    Pages 67-83

    Willoughby, D. A. (et al.)

  • NSAID mechanism of action: the role of intracellular pharmacokinetics

    Pages 85-102

    Herbette, L. G. (et al.)

Buy this book

eBook $109.00
price for USA in USD
  • ISBN 978-94-010-9029-2
  • Digitally watermarked, DRM-free
  • Included format: PDF
  • ebooks can be used on all reading devices
  • Immediate eBook download after purchase
Softcover $139.00
price for USA in USD
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Bibliographic Information

Bibliographic Information
Book Title
Improved Non-Steroid Anti-Inflammatory Drugs: COX-2 Enzyme Inhibitors
Editors
  • Sir John R. Vane
  • Jack Botting
  • R.M. Botting
Copyright
1996
Publisher
Springer Netherlands
Copyright Holder
Kluwer Academic Publishers and William Harvey Press
eBook ISBN
978-94-010-9029-2
DOI
10.1007/978-94-010-9029-2
Softcover ISBN
978-94-010-9031-5
Edition Number
1
Number of Pages
200
Topics