Antithrombotic activity and the mechanism of action of trapidil (Rocornal).

Antithrombotic activity and the mechanism of action of trapidil were investigated, as compared with those of aspirin and dipyridamole. Trapidil at oral doses of 30 and 100 mg/kg inhibited arterial thrombosis in rats, while aspirin and dipyridamole at doses up to 300 mg/kg showed only a mild activity. This action may be explained by the fact that trapidil at concentrations ranging from 139 microM to 251 microM exerted 50% inhibition of platelet aggregation induced by ADP, arachidonic acid, thrombin or thromboxane A2 mixture, inhibition of platelet release reaction induced by ADP, arachidonic acid or thrombin, disaggregatory effect on aggregated rabbit platelets by arachidonic acid and potentiating action on antiaggregatory action of prostacyclin in vitro. In vitro actions of trapidil were apparently different from those of aspirin and dipyridamole. Trapidil also showed inhibition of platelet phosphodiesterase activity and thromboxane synthetase activity. Trapidil was expected to be an effective antithrombotic agent. The antithrombotic action of trapidil may be mediated by the inhibition of platelet function which is characterized by the inhibition of both thromboxane synthetase and phosphodiesterase activities, and by the potentiation of the antiaggregatory action of prostacyclin.