Advertisement

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

  • John Vane
  • Jack Botting
  • Regina Botting

Table of contents

  1. Front Matter
    Pages i-ix
  2. D. A. Willoughby, A. Tomlinson, D. Gilroy, D. Willis
    Pages 67-83
  3. L. G. Herbette, M. Vecchiarelli, G. Trummlitz
    Pages 85-102
  4. C. Patrono, P. Patrignani, M. R. Panara, F. Cipollone, G. Santini, M. G. Sciulli et al.
    Pages 121-131
  5. P. Bennett, D. Slater
    Pages 167-188
  6. D. N. Bateman
    Pages 189-201
  7. J. C. Frölich, D. O. Stichtenoth
    Pages 203-228
  8. Back Matter
    Pages 243-248

About this book

Introduction

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.

Keywords

cardiovascular disease inflammation kidney kinetics pharmacokinetics pharmacology research toxicity

Editors and affiliations

  • John Vane
    • 1
  • Jack Botting
    • 1
  • Regina Botting
    • 1
  1. 1.The William Harvey Research InstituteSaint Bartholomew’s Hospital Medical CollegeLondonUK

Bibliographic information

  • DOI https://doi.org/10.1007/978-94-010-9029-2
  • Copyright Information Springer Science+Business Media B.V. 1996
  • Publisher Name Springer, Dordrecht
  • eBook Packages Springer Book Archive
  • Print ISBN 978-94-010-9031-5
  • Online ISBN 978-94-010-9029-2
  • Buy this book on publisher's site