cyclo-oxygenase 1 and cyclo-oxygenase 2

Last reviewed 07/2021

  • non-steroidal anti-inflammatory drug (NSAID)s are thought to work via inhibition of the enzyme, cyclo-oxygenase (COX), also known as prostaglandin synthetase
    • NSAIDs are a heterogeneous class including aspirin and various other nonselective and selective inhibitors of cyclooxygenase (COX). Aspirin is the only NSAID used for prevention and treatment of coronary heart disease (CHD)

  • cyclo-oxygenase is present in different forms - the two isoforms are encoded by different genes and have unique patterns of expression:
    • cyclo-oxygenase 1 (COX1)
      • COX-1 isozyme is essential for the maintenance of normal physiologic states in many tissues including the kidney, gastrointestinal tract, and platelets - for example, COX-1 activation in the gastric mucosa leads to prostaglandin PGI2 (prostacyclin) production, which is cytoprotective
      • thromboxane A2, which is primarily synthesized in platelets through COX-1 activity, causes platelet aggregation, vasoconstriction, and smooth muscle proliferation
    • cyclo-oxygenase 2 (COX2) is less widely expressed, but is readily induced by pro-inflammatory stimuli, and catalyses production of prostaglandins that mediate inflammation
    • inhibition of COX-1 is thought to be the main way in which NSAIDs cause gastrointestinal damage
      • anti-inflammatory efficacy is believed to result from inhibition of COX-2
      • at therapeutic doses, COX-2 inhibitors inhibit COX-2 but not COX-1, so it was postulated that they should relieve inflammation with less gastrointestinal toxicity than conventional NSAIDs
      • it now is apparent that selective inhibition of COX-2 appears more complex than first suggested, as COX-2 has many other functions besides its role in inflammation
        • in vascular endothelium, it mediates production of prostaglandin PGI2 (prostacyclin), a vasodilator and inhibitor of both platelet aggregation and proliferation of vascular smooth muscle cells
        • therefore in consideration that COX-1 mediates synthesis of thromboxane A2 (vasoconstrictor and stimulator of both platelet aggregation and vascular proliferation) both isoforms are probably important in vascular homeostasis and regulation of platelet function


  1. Prescribers' Journal (1999); 39 (2): 102-8.
  2. Drug and Therapeutics Bulletin (2005); 43(1):1-6.