Potentiation by dazoxiben, a thromboxane synthetase inhibitor, of platelet aggregation inhibitory activity of a thromboxane receptor antagonist and of prostacyclin.

Dazoxiben, a thromboxane (Tx)-synthetase inhibitor, completely prevented platelet TxB2 synthesis, but not the platelet aggregation induced by arachidonic acid (AA) or ADP. It was also ineffective against platelet aggregation brought about by a prostaglandin (PG) endoperoxide analogue, which does not trigger platelet TxA2 synthesis. The association of dazoxiben with a Tx receptor antagonist or with PGI2 resulted in marked potentiation of the latter compounds as inhibitors of platelet aggregation induced by AA or ADP (second wave), but not by U-46619 (a stable analogue of prostaglandin endoperoxides). It therefore appears that inhibition of Tx synthesis does not modify the platelet response to aggregating stimuli but renders platelets more susceptible to inhibition induced by other compounds.