title: Distribution and expression of cyclooxygenase (COX) isoenzymes, their physiological roles, and the categorization of nonsteroidal anti-inflammatory drugs (NSAIDs).
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.
authors.affiliation: Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Wallace
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000068579:Celecoxib; D018849:Controlled Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D017308:Etodolac / Q000009:adverse effects; D015870:Gene Expression; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects; D007213:Indomethacin / Q000009:adverse effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D000077239:Meloxicam; D008565:Membrane Proteins; D009288:Naproxen / Q000009:adverse effects; D009578:Nitrobenzenes / Q000009:adverse effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects; D013843:Thiazines / Q000009:adverse effects; D013844:Thiazoles / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011720:Pyrazoles; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D017308:Etodolac; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; C012655:nimesulide; D000077239:Meloxicam; D007052:Ibuprofen; D007213:Indomethacin