Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy.
Cyclo-oxygenase is expressed in cells in two distinct isoforms. Cyclo-oxygenase-1 is present constitutively whilst cyclo-oxygenase-2 is expressed primarily after inflammatory insult. The activity of cyclo-oxygenase-1 and -2 results in the production of a variety of potent biological mediators (the prostaglandins) that regulate homeostatic and disease processes. Inhibitors of cyclo-oxygenase include the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, ibuprofen and diclofenac. NSAIDs inhibit cyclo-oxygenase-2 at the site of inflammation, to produce their therapeutic benefits, as well as cyclo-oxygenase-1 in the gastric mucosa, which produces gastric damage. Most recently selective inhibitors of cyclo-oxygenase-2 have been developed and introduced to man for the treatment of arthritis. Moreover, recent epidemiological evidence suggests that cyclo-oxygenase inhibitors may have important therapeutic relevance in the prevention of some cancers or even Alzheimer's disease. This review will discuss how the new advancements in NSAIDs research has led to the development of a new class of NSAIDs that has far reaching implications for the treatment of disease.
Mitchell
J A
JA
Unit of Critical Care Medicine, Royal Brompton Hospital, Imperial College School of Medicine, Sydney Street, London SW3 6NP. j.a.mitchell@ic.ac.uk
Warner
T D
TD
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D051546:Cyclooxygenase 2; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases