Distribution and expression of cyclooxygenase (COX) isoenzymes, their physiological roles, and the categorization of nonsteroidal anti-inflammatory drugs (NSAIDs)

Am J Med. 1999 Dec 13;107(6A):11S-16S; discussion 16S-17S. doi: 10.1016/s0002-9343(99)00363-0.

Abstract

The molecular identification of a second isoform of cyclooxygenase-2 (COX-2) led to a major investment by several pharmaceutical companies in the development of selective inhibitors. The central tenets of the rationale for developing selective COX-2 inhibitors are that prostaglandins that contribute to inflammation are derived from COX-2, whereas prostaglandins that are involved in normal physiological processes are derived from the constitutively expressed isoform COX-1. There is now considerable evidence that COX-2 is actually expressed constitutively in many tissues and performs important physiological functions. Thus, suppression of COX-2 with selective inhibitors should not be expected to be without some adverse consequences. Moreover, there is strong evidence that COX-1 contributes to inflammation and pain, so selective inhibition of COX-2 will not necessarily produce the same degree of efficacy that is seen with mixed inhibitors of COX-1 and COX-2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Celecoxib
  • Controlled Clinical Trials as Topic
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / adverse effects*
  • Etodolac / adverse effects
  • Gene Expression
  • Humans
  • Ibuprofen / adverse effects
  • Indomethacin / adverse effects
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Isoenzymes / pharmacology
  • Meloxicam
  • Membrane Proteins
  • Naproxen / adverse effects
  • Nitrobenzenes / adverse effects
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandin-Endoperoxide Synthases / pharmacology
  • Pyrazoles
  • Sulfonamides / adverse effects
  • Thiazines / adverse effects
  • Thiazoles / adverse effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Nitrobenzenes
  • Pyrazoles
  • Sulfonamides
  • Thiazines
  • Thiazoles
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Etodolac
  • Naproxen
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib
  • nimesulide
  • Meloxicam
  • Ibuprofen
  • Indomethacin