Phenothiazine compounds enhance phentolamine effects on platelet aggregation and thromboxane B2 production

In the present study we investigated the influence of phentolamine and the phenothiazine compounds chlorpromazine and trifluoperazine on human platelet aggregation as well as the effect of the association of phentolamine and the phenothiazines on responses to adenosine diphosphate, collagen, thrombin, ionophore A23187 and phorbol-myristate acetate, release reaction, thromboxane B2 synthesis and intraplatelet cyclic adenosine monophosphate levels. Phentolamine and phenothiazines exerted a dose-dependent inhibitory effect on aggregation induced by different concentrations of adenosine diphosphate and decreased the response to other agonists; furthermore, the phenothiazines enhanced the inhibitory effects of phentolamine on aggregation and thromboxane B2 synthesis, without influencing intraplatelet cyclic adenosine monophosphate levels. Phorbol ester-induced platelet activation was also inhibited in a dose-dependent way by each compound and by an association of phentolamine and phenothiazines, suggesting that the antiplatelet properties of these compounds might also be ascribed to intracellular events.