title: In vitro and in vivo pharmacological evidence of selective cyclooxygenase-2 inhibition by nimesulide: an overview.
abstract: Most available nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both the constitutive cyclooxygenase-1 (COX-1) and the inducible cyclooxygenase-2 (COX-2), resulting in inhibition of prostaglandin (PG) and thromboxane (TX) biosynthesis. The inhibition of COX-2 might be the cause of the favourable anti-inflammatory, analgesic and antipyretic effects of NSAIDs, whereas that of COX-1 might result in unwanted gastrointestinal, renal and possibly other side-effects. Nimesulide is a sulfonanilide compound with anti-inflammatory properties. Its pharmacological profile (better inhibition of PG synthesis in inflammatory areas than in gastric mucosa), suggested that it might be a selective inhibitor of COX-2. In several in vitro assays using either purified COX-2 and COX-1 preparations or cell preparations (both from animal and human origins) expressing COX-1 or COX-2, ten out of eleven different groups have demonstrated that nimesulide selectively inhibits COX-2. The COX-2/ COX-1 inhibitory ratio varies, according to the assay preparation, from about 0.76 to 0.0004 i.e. a 1.3 to 2,512-fold higher selectivity for COX-2 than for COX-1. Moreover, an in vivo whole blood assay performed on healthy volunteers demonstrated a significant fall in COX-2 PGE2 production without any effect on COX-1 TXB2 production in subjects treated with nimesulide (100 mg b.i.d. for 2 weeks) versus no effect on COX-2 PGE2 and an almost total suppression of COX-1 TXB2 in subjects treated with aspirin (300 mg t.i.d. for 2 weeks). Nimesulide can thus be considered a relatively selective COX-2 inhibitor. At the recommended dosage of 100 mg b.i.d., it is as effective an analgesic and anti-inflammatory agent as classical NSAIDs, and a well-tolerated drug with few side-effects according to large-scale open studies and a global evaluation of a large number of controlled and non-controlled comparative trials.
authors.affiliation: Therabel Research S.A., Brussels, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Famaey
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013449:Sulfonamides; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C012655:nimesulide