Influence of benzamidine derivatives on thrombin-induced platelet reactions.

The influence of competitive synthetic thrombin inhibitors of the benzamidine type on the thrombin-platelet reaction was studied. The benzamidine derivatives tested inhibited thrombin-induced aggregation and 5-HT release in dependence upon their affinity for the enzyme. Accumulation of platelets in the lung of rats and the fall in platelet counts in the blood of rabbits induced by thrombin infusion were prevented by infusion of the inhibitors, as illustrated by example of 3-TAPAP. The thrombin-platelet reaction was inhibited at higher doses of inhibitor than those required for inhibition of coagulation. In this way, the inhibitors may exert a different influence on the various haemostatic steps.