Studies on the safety of a new non-steroidal anti-inflammatory drug: protacine (CR 604).
The effects of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazinyl-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate(protacine, CR 604) on gastrointestinal physiology and tolerance were investigated. The anti-inflammatory activities and the effects on the gastrointestinal tract showed a very good separation. Protacine showed a smaller influence on gastric prostaglandins and did not stimulate both basal and cAMP enhanced gastric acid output as did other antiinflammatory drugs. This may explain, at least in part, its gastrointestinal safety. Articular cartilage metabolism showed to remain practically unchanged by protacine both in in vitro and ex vivo experiments. All these results show that protacine has very good gastrointestinal safety indexes, that effects on articular cartilage metabolism are very low and that, from these points of view, it is superior to other non-steroidal anti-inflammatory drugs of similar potency.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D002358:Cartilage, Articular / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005750:Gastric Juice / Q000378:metabolism; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000633:toxicity*; D007700:Kinetics; D010879:Piperazines / Q000633:toxicity; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D013270:Stomach / Q000166:cytology; D013276:Stomach Ulcer / Q000139:chemically induced
D000893:Anti-Inflammatory Agents; D007210:Indoleacetic Acids; D010879:Piperazines; D011453:Prostaglandins