Mediation of inflammation by cyclooxygenase-2

Agents Actions Suppl. 1995:46:41-50. doi: 10.1007/978-3-0348-7276-8_5.

Abstract

Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used for the treatment of inflammation, pain, and fever. Mechanistically, these compounds are believed to act via inhibition of the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDS are efficacious antiinflammatory agents, significant side effects limit their use. Recently two forms of COX were identified- a constitutively expressed COX-1 and a cytokine-inducible COX-2. Commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2 suggesting the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1) in normal tissues, whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2, at the site of inflammation. Therefore, a selective inhibitor of COX-2 may be anti-inflammatory without GI toxicity-providing a significant improvement over currently available NSAIDs.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / enzymology
  • Cyclooxygenase Inhibitors / pharmacology
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / enzymology
  • Isoenzymes / physiology*
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • Pyrazoles / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Pyrazoles
  • 1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
  • Prostaglandin-Endoperoxide Synthases