ISSN:
1432-1041
Keywords:
Naftopidil
;
Serotonin
;
5-Hydroxytryptamine
;
platelets
;
aggregation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Naftopidil exerts its antihypertensive action via α1-adrenoceptor blockage and Ca2+ 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 μM, the pIC50 was 5.09 with induction of aggregation by 1 μM 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-HT-induced 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-HT inhibitory action of naftopidil adds a third possible antihypertensive property to naftopidil's α1-adrenoceptor blocking and Ca2+ antagonistic properties.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00192561
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