Pharmacological study of a new non-steroidal anti-inflammatory drug: protacine (CR 604).
The pharmacological activities of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropylglutaramate(+/-)dimaleate (protacine, CR 604), a new indolyl derivative with strong anti-inflammatory, analgesic and antipyretic activities, are described. The dose-dependent activity of protacine on inflammation has been shown both in short-term experiments, like the hind paw edema induced by carrageenin and several other irritants, and long-term tests, like the aminoacetonitrile-induced osteolathyrism, the adjuvant-induced arthritis and the cotton pellet-induced granuloma. The analgesic activity of the drug has been evidenced in the phenylquinone-induced writhing and the Randall-Selitto tests, and the antipyretic effects in the yeast-induced hyperthermia in rats. Other general pharmacological effects have been studied, too. Contrarily to several other anti-inflammatory drugs, including indometacin, showing advers effects at doses which are in the same range of those active on experimental inflammation, protacine shows these effects to a minor degree and at doses which are much larger than those pharmacologically active. The therapeutic index of protacine therefore is superior to that of other anti-inflammatory drugs.
D000607:Aminoacetonitrile / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001169:Arthritis, Experimental / Q000188:drug therapy; D002490:Central Nervous System / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004487:Edema / Q000188:drug therapy; D005260:Female; D006099:Granuloma; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000494:pharmacology* / Q000633:toxicity; D007842:Lathyrism / Q000188:drug therapy; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology / Q000633:toxicity; D011817:Rabbits; D051381:Rats
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D010879:Piperazines; D000607:Aminoacetonitrile