Naftopidil exerts its antihypertensive action via al-adrenoceptor blockage and Ca 2+ antagonism in vascular smooth muscle. Since the chemically similar 1 -(1-naphthyl) piperazine is known to be a 5-hydroxytryptamine2 receptor antagonist, the 5-hydroxytryptamine (5-HT) antagonistic properties of naftopidil were tested by examining 5-HT-induced aggregation and 5-HT uptake in platelets from 12 healthy volunteers after oral administration of 60 mg naftopidil or placebo.
Platelet aggregation in vitro was inhibited by naftopidil with a Ki value of 1.1 gM, the pICs0 was 5.09 with induction of aggregation by 1 ~tM 5-HT. After oral administration of naftopidil, 5-HT-induced aggregation was significantly inhibited by 36 %. 4 h after naftopidil administration, 5-HT uptake velocity was reduced by 33 %. Naftopidil not only cancelled the circadian increase in 5-HTinduced aggregation velocity observed during placebo application, but also caused a decrease in aggregation velocity directly after peak plasma naftopidil levels. 5-HT uptake in platelets was also reduced following peak naftopidil plasma concentrations. The 5-HTinhibitory action of naftopidil adds a third possible antihypertensive property to naftopidil's al-adrenoceptor blocking and Ca 2 + antagonistic properties.