Pharmacodynamics of Agacutin: a thrombin-like enzyme from Agkistrodon acutus

Objective To investigate the effects of Agacutin on blood system and evaluate its hemostatic action in animals.Methods The indexes on blood coagulation and fibrinolysis system were determined after Agacutin was administerted intravenously, with blood samples taken by cardiac puncture. The hemostatic effect was expressed in terms of the mouse tail bleeding time.Results Intravenous injection of Agautin 0.01-0.05 U·kg~ -1 could markedly shorten the rabbit blood coagulation time by 44.9%-60.5% and the effect lasted for 24 h. When Reptilase and Agacutin were administered in the same dosage, their effects on blood coagulation were about equal in strength and duration. After Agacutin iv, the rabbit blood fibrinogen level and blood viscosity were decreased, which persisted in parallel with the shortening of blood coagulation time. Experimental results also showed that Agacutin had no influence on activated partial thromboplastin time (APTT), platelet count, platelet releasing activity, platelet in vitro aggregation,and euglobulin coagulation time (ECT). But the shortening of euglobulinolysis time (ELT) suggested that Agacutin have a weak fibrinolytic activity. Intraperitoneal administration of Agacutin 0.5-2.0 U·kg~ -1 could shorten the mouse tail bleeding time by 24%-66%.Conclusion The results show that Agacutin elevates the level of soluble fibrin in blood vessel and does not activate prothrombin (factor Ⅱ) or factor . Agacutin promotes hemostasis only when there is a cut or bleeding.The soluble fibrin induced in normal vessel will not form insoluble fibrin clot or thrombosis in vivo. The present study shows that Agacutin is a potential hemostatic agent, having no undesirable effects on otherwise normal blood coagulation.