Anti-inflammatory, analgesic, and antipyretic effects and gastrointestinal toxicity of the new anti-inflammatory 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-chlorobenzoyl) 5-methoxy-2-methyl-3-indolylacetate (CP-331, CAS 127966-70-5), a new anti-inflammatory drug, were evaluated using indomethacin 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 indomethacin. In addition, CP-331 influenced more markedly than indomethacin 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 indomethacin. 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.
Segawa
Y
Y
Department of Pharmacology, Zeria Pharmaceutical Co., Ltd. Saitama, Japan.
Ohya
O
O
Abe
T
T
Omata
T
T
Tsuzuike
N
N
Itokazu
Y
Y
Yoshida
K
K
Tagashira
E
E
Ueda
I
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004890:Erythema / Q000517:prevention & control; D005753:Gastric Mucosa / Q000187:drug effects; D006099:Granuloma / Q000517:prevention & control; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C069844:CP 331; D007213:Indomethacin