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Anti-Inflammatory Drugs

New clues in the COX2 mystery

Nature Reviews Drug Discovery volume 5, page 4571 (2006)Cite this article

The development of selective COX2 inhibitors was initially stimulated by the hypothesis that COX1 was a constitutively expressed isoform whose inhibition could cause the gastrointestinal side effects characteristic of traditional nonsteroidal anti-inflammatory drugs (NSAIDs), whereas COX2 was an inducible isoform whose inhibition results in the anti-inflammatory effects of these drugs. However, the hypothesis seems over-simplistic in the light of the problems with COX2 inhibitors, and considerable attention is now being focused on gaining a deeper understanding of the mechanisms underlying the beneficial and adverse effects of COX inhibition.

A key to understanding these effects seems to be the relative influence of COX1 and COX2 inhibition on the levels of the various prostanoids that result from further enzymatic modification of the product of both COX enzymes, prostaglandin H2. For example, suppression of the production of the prostanoid prostaglandin E2 is believed to underlie the anti-inflammatory efficacy of COX2 inhibitors. However, it has been proposed that concomitant alterations of the levels of other prostanoids — thromboxane A2, which has prothrombotic effects, and prostacyclin, which has antithrombotic effects — might cause cardiovascular side effects.

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References

ORIGINAL RESEARCH PAPER

  1. Cheng, Y. et al. Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function. J. Clin. Invest. 116, 1391–1399 (2006)

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FURTHER READING

  1. Mitchell, J. A., Warner, T. D. COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nature Rev. Drug Discov. 5, 75–86 (2006)

    Article  CAS  Google Scholar 

  2. Grosser, T., Fries, S. & FitzGerald, G. A. et al. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. Clin. Invest. 116, 4–15 (2006)

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Authors
  1. Peter Kirkpatrick
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Kirkpatrick, P. New clues in the COX2 mystery. Nat Rev Drug Discov 5, 4571 (2006). https://doi.org/10.1038/nrd2061

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