[Cyclooxygenase (COX)-2 selective inhibitors: aspirin, a dual COX-1/COX-2 inhibitor, to COX-2 selective inhibitors].
Aspirin was developed as a non-steroidal anti-inflammatory drug (NSAID) in 1899. During the century after that, aspirin has been found to show its anti-inflammatory, analgesic and anti-pyretic activities by reducing prostaglandins biosynthesis through inhibition of cyclooxygenase (COX); and then COX was found to be constituted of two isoforms, constitutive COX-1 and inducible COX-2. Currently, novel NSAIDs, acting through selective inhibition of COX-2, that have efficacy as excellent as aspirin with significantly lower incidence of gastrointestinal adverse effects are available in America and some other countries, but not in Japan. Physiological and pathophysiological roles of COX-1 and COX-2 have been explained from studies in experimental animals, but there are many differences in species and diseases between animals and humans. Thus, physiological and pathophysiological roles of COX-2 were considered from the standpoint of clinical effects of the two latest COX-2 selective inhibitors, celecoxib and rofecoxib, on inflammation, pain, fever and colorectal cancer together with their adverse effects on gastrointestinal, renal and platelet functions; and the usefulness and limits of COX-2-selective inhibitors were discussed with the trends of new NSAIDs development.
Nakamura
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Center of Pharmacovigilance & Regulatory Affairs, Dainippon Pharmaceutical Co., Ltd., 2-6-8 Dosho-machi, Chuo-ku, Osaka 541-0045, Japan. hideo-nakamura@dainippon-pharm.co.jp
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000068579:Celecoxib; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000517:prevention & control; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005334:Fever / Q000188:drug therapy; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D008565:Membrane Proteins; D010146:Pain / Q000188:drug therapy; D010437:Peptic Ulcer / Q000139:chemically induced; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D001241:Aspirin