[Pharmacological studies of FUT-175, nafamstat mesilate. IV. Effects on coagulation, platelets and fibrinolysis].
Inhibitory effects of FUT-175 (nafamstat mesilate) on coagulation, platelets and fibrinolysis were examined. FUT-175 prolonged activated partial thromboplastin time, thrombin time and prothrombin time in rabbit plasma. FUT-175 prolonged these coagulation times in human plasma at lower concentration than in rabbit plasma. FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents in rabbit platelet-rich plasma (PRP). In human PRP, FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents at lower concentration than in rabbit PRP. Lipopolysaccharide induced a dose-dependent platelet aggregation in dog PRP. FUT-175 showed an inhibitory effect on this aggregation. FUT-175 inhibited clot retraction in rabbit plasma. The fibrinolysis activity was measured on fibrinolysis of rabbit plasma activated by urokinase. FUT-175 prolonged this fibrinolysis time. Inhibitory effects on coagulation and fibrinolysis were also found ex vivo. FUT-175 prolonged bleeding time in mice. These results indicate that FUT-175 has potent inhibitory effects on coagulation, platelets and fibrinolysis.
D000818:Animals; D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D001550:Benzamidines; D001760:Bleeding Time; D003018:Clot Retraction; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013045:Species Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D001550:Benzamidines; D006146:Guanidines; D008070:Lipopolysaccharides; D014568:Urokinase-Type Plasminogen Activator; C032855:nafamostat