Anticoagulant and antithrombotic action of the synthetic thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginine nitrile.
Anticoagulant and antithrombotic effects of a synthetic thrombin inhibitor of the tripeptide type, D-phenylalanyl-L-prolyl-L-arginine nitrile (1), were studied in vitro and in vivo. The anticoagulant action was investigated in common test assays such as thrombin time, activated partial thromboplastin time, prothrombin time and thrombelastography. In human plasma 1 caused a concentration-dependent prolongation of coagulation times and influenced the recalcification measured by thrombelastographic recording. In different models of experimental thrombosis in rats the antithrombotic effectiveness of 1 was shown. I.v. infusion of the thrombin inhibitor reduced or prevented the formation of stasis-induced venous thrombi and of arterial thrombi after electrically induced damage of the vessel wall as well as prolonged the time of a thrombotic occlusion of an extracorporeal arterio-venous shunt. At low doses 1 was also effective in thrombin-induced microthrombosis.
Kaiser
B
B
Institute of Pharmacology and Toxicology, Medical Academy Erfurt.
Richter
M
M
Hauptmann
J
J
Markwardt
F
F
D000818:Animals; D000925:Anticoagulants; D001777:Blood Coagulation / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000097:blood / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; C055799:phenylalanyl-prolyl-arginine nitrile; D013917:Thrombin