COX-1 and COX-3 inhibitors

Thromb Res. 2003 Jun 15;110(5-6):269-72. doi: 10.1016/s0049-3848(03)00411-0.


Low doses of aspirin reduce both pain and fever, whereas the anti-inflammatory action of aspirin requires a much higher dose. It is possible that inhibition of cyclooxygenase (COX)-1 is the major action of aspirin involved in its analgesic and antipyretic effects, and inhibition of COX-2 is responsible for its anti-inflammatory action. We compared the analgesic effects of an aspirin-like drug (diclofenac) and a centrally acting analgesic (paracetamol) in the mouse stretching test and confirmed that the analgesic action of the aspirin-like drug was peripheral. Two possible sites have been postulated for the antipyretic action of non-steroid anti-inflammatory drugs; (a) inhibition of COX in endothelial cells of hypothalamic blood vessels or (b) inhibition of COX synthesising prostaglandins near sensory receptors of sub-diaphragmatic vagal afferents. The antipyretic action of aspirin may be mediated by inhibition of COX-3 in hypothalamic endothelial cells or by inhibition of COX-1 localised close to sensory receptors of peripheral vagal afferents. It is also possible that both enzymes are involved in the antipyretic action of aspirin. Whereas lipopolysaccharide (LPS)-induced fever is attenuated in COX-2 gene-deleted mice, suggesting that COX-2 is responsible for this type of fever, the COX-1 gene may also be important in temperature regulation and in mediating the pyresis that occurs in the absence of infection.

Publication types

  • Review

MeSH terms

  • Analgesics, Non-Narcotic / administration & dosage
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Aspirin / administration & dosage*
  • Cyclooxygenase 1
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Dogs
  • Dose-Response Relationship, Drug
  • Fever / drug therapy
  • Fever / metabolism*
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism*
  • Membrane Proteins
  • Mice
  • Pain / drug therapy
  • Pain / metabolism*
  • Prostaglandin-Endoperoxide Synthases / metabolism*


  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 1
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, mouse
  • cyclooxygenase-3
  • Aspirin