Antithrombotic effects of YS-49 and YS-51-1-naphthylmethyl analogs of higenamine

초록

The antiplatelet and antithrombotic effects of YS-49 and YS-51-1-naphthylmethyl analogs of higenamine, which is a benzyl-tetrahydroisoquinoline alkaloid isolated from Aconitum japonicum (Ranunculaceae) - were investigated. YS-49 and YS-51 showed inhibitory activities to both human and rat platelet aggregation induced by ADP, collagen and epinephrine. They were more inhibitory to epinephrine-induced aggregation (IC50; 3.4 and 1.7 muM of YS-49, and 6.0 and 6.3 muM of YS-51 to human and rat platelets, respectively) than ADP- or collagen-induced aggregation. The antithrombotic effects of YS-49 and YS-51 were also observed in both mouse acute thrombosis model and rat arterio-venous shunt (AV shunt) model. The oral administration of YS-49 and YS-51 (50 or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in mice and lowered the weight of thrombus formed inside the AV shunt tube in rats. (C) 2001 Elsevier Science Ltd. All rights reserved.

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