NAFTOPIDIL INHIBITS 5-HYDROXYTRYPTAMINE-INDUCED PLATELET-AGGREGATION AND 5-HYDROXYTRYPTAMINE UPTAKE IN PLATELETS OF HEALTHY-VOLUNTEERS

Naftopidil exerts its antihypertensive action via alpha(1)-adrenocepto r blockage and Ca2+ antagonism in vascular smooth muscle. Since the ch emically similar 1-(1-naphthyl) piperazine is known to be a 5-hydroxyt ryptamine(2) receptor antagonist, the 5-hydroxytryptamine (5-HT) antag onistic properties of naftopidil were tested by examining 5-HT-induced aggregation and 5-HT uptake in platelets from 12 healthy volunteers a fter oral administration of 60 mg naftopidil or placebo. Platelet aggr egation in vitro was inhibited by naftopidil with a K-i value of 1.1 m u M, the pIC(50) was 5.09 with induction of aggregation by 1 mu M 5-HT . After oral administration of naftopidil, 5-HT-induced aggregation wa s significantly inhibited by 36 %. 4 h after naftopidil administration , 5-HT uptake velocity was reduced by 33 %. Naftopidil not only cancel led the circadian increase in 5-HT-induced aggregation velocity observ ed during placebo application, but also caused a decrease in aggregati on velocity directly after peak plasma naftopidil levels. 5-HT uptake in platelets was also reduced following peak naftopidil plasma concent rations. The 5-HT inhibitory action of naftopidil adds a third possibl e antihypertensive property to naftopidil's alpha(1)-adrenoceptor bloc king and Ca2+ antagonistic properties.