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. 1) FUT-175 prolonged activated partial thromboplastin time, thrombin time and prothrombin time in rabbit plasma. 2) FUT-175 prolonged these coagulation times in human plasma at lower concentration than in rabbit plasma. 3) FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents in rabbit plateletrich plasma (PRP). 4) In human PRP, FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents at lower concentration than in rabbit PRP. 5) Lipopolysaccharide induced a dose-dependent platelet aggregation in dog PRP. FUT-175 showed an inhibitory effect on this aggregation. 6) FUT-175 inhibited clot retraction in rabbit plasma. 7) The fibrinolysis activity was measured on fibrinolysis of rabbit plasma activated by urokinase. FUT-175 prolonged this fibrinolysis time. 8) Inhibitory effects on coagulation and fibrinolysis were also found ex vivo. 9) FUT-175 prolonged bleeding time in mice. These results indicate that FUT-175 has potent inhibitory effects on coagulation, platelets and fibrinolysis.