[Anti-inflammatory, analgesic and antipyretic actions of 1-(m-chlorophenyl)-3-N, N-dimethylcarbamoyl-5-methoxypyrazole (PZ-177)].
We have reported that PZ-177 was found to have potent inhibitory activity on acute inflammatory edema. In this paper, the anti-inflammatory, analgesic and antipyretic properties of PZ-177 were assessed by a battery of standard tests. PZ-177 inhibited the increased vascular permeability induced by histamine, xylene and acetic acid. The activity was the same as the anti-edematous one and was more potent than that of mepirizole. PZ-177 did not inhibit ultraviolet erythema in guinea pigs, proliferation of granulation tissue in cotton pellet and granuloma pouch tests of rats and adjuvant arthritis in rats. Wound healing was not prolonged and the agent was weak in ulcerogenic action. PZ-177 did not affect heat denaturation of bovine serum albumin at pH 5.3, but inhibited hyperthermic hemolysis at pH 7.4 and exerted a stabilizing effect on biological membranes. This is considered to be one of the mechanisms of action. When analgesic action was tested by the writhing and Haffner's methods in mice, the compound revealed a more potent activity than did mepirizole and aminopyrine. Utilizing the Randall-Selitto's analgesic method in rats, a significant rise in pain threshold was obtained only at the inflamed foot. The antipyretic action was less than aminopyrine in febrile rabbits. From the above results, PZ-177 may be classified as a potent analgesic and anti-inflammatory agent but has no effect on proliferation of granulation tissue and chronic inflammatory disease.
D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D004890:Erythema / Q000188:drug therapy; D005260:Female; D006099:Granuloma / Q000188:drug therapy; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D014945:Wound Healing / Q000187:drug effects
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles