ANTIINFLAMMATORY, ANALGESIC, AND ANTIPYRETIC EFFECTS AND GASTROINTESTINAL TOXICITY OF THE NEW ANTIINFLAMMATORY DRUG N-(3-[3-(PIPERIDINYLMETHYL)PHENOXY]PROPYL)-CARBAMOYLMETHYLTHIO]ETHYL 1-(P-CHLOROBENZOYL) 5-METHOXY-2-METHYL-3-INDOLYLACETATE

The anti-inflammatory, analgesic, and antipyretic effects and gastrointestinal toxicity of N-{3-[3-(piperidinylmethyl) phenoxy] propyl} carbamoylmethylthio] ethyl 1-(p-chlorobensoyl) 5-methoxy-2-methyl-3-indolylacetate (CP-331, CAS 127966-70-5), a new anti-inflammatory drug, were evaluated using indometacin as a control. CP-331 exerted anti-inflammatory, analgesic and antipyretic effects on the models of carrageenin-induced paw edema, increased vascular permeability, ultraviolet light-induced erythema, granuloma proliferation, adjuvant arthritis, inflammatory pain, and yeast-induced fever. However, these effects were observed at a molar level similar to or higher than that of indometacin. In addition, CP-331 influenced more markedly than indometacin the delayed type hypersensitivity to sheep red blood cells. On the other hand, CP-331 did not damage the gastric mucosa even at a high dose of 1,000 mg/kg and also induced slighter damage to the intestinal mucosa than indometacin. Thus, CP-331 exerted anti-inflammatory, analgesic, and antipyretic effects but without showing gastric toxicity, which is a common side effect of anti-inflammatory drugs. These results suggest the clinical applicability of this drug in the long-term therapy of inflammatory diseases such as rheumatoid arthritis.