In vitro studies of a new synthetic thrombin inhibitor.
(2R, 4R)4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8-quinoline- sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 microM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10(-4) M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.
D001120:Arginine / Q000031:analogs & derivatives; D002118:Calcium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010875:Pipecolic Acids / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors*
D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban; D002118:Calcium