Studies on the mechanism of action of protacine (CR 604), a new non-steroidal anti-inflammatory agent.
3'-(4-[2-(1-P-Chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate (protacine, CR 604), a new non-steroidal compound active on experimental inflammation, in vitro inhibits prostaglandin synthesis from arachidonic acid and platelet aggregation. When administered p.o., it prevents ex vivo platelet aggregation and in vivo arachidonate-induced thrombosis in rabbits. The cAMP levels of rat leucocytes are significantly reduced after treatment in vivo with protacine, even under maximum PGE-mediated stimulation. These effects, the inhibition of the proteolytic activity of trypsin and the fibrinolytic properties evidenced on recalcified plasma clots, contribute to explain the anti-inflammatory activity of protacine.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism; D009129:Muscle Tonus / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013927:Thrombosis / Q000503:physiopathology; D014361:Trypsin Inhibitors
D000893:Anti-Inflammatory Agents; D007210:Indoleacetic Acids; D010879:Piperazines; D011453:Prostaglandins; D014361:Trypsin Inhibitors; D000242:Cyclic AMP