Naftopidil inhibits 5-hydroxytryptamine-induced platelet aggregation and 5-hydroxytryptamine uptake in platelets of healthy volunteers.
Naftopidil exerts its antihypertensive action via alpha 1-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 microM, the pIC50 was 5.09 with induction of aggregation by 1 microM 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 alpha 1-adrenoceptor blocking and Ca2+ antagonistic properties.
Kirsten
R
R
Department of Clinical Pharmacology, University of Frankfurt, Main, Germany.
Breidert
M
M
Nelson
K
K
Heine
A
A
Rosenkranz
S
S
Erdeg
B
B
Niebch
G
G
Borbe
H O
HO
Siebert-Weigel
M
M
Respondek
J
J
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000009:adverse effects / Q000494:pharmacology*; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009281:Naphthalenes; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C064357:naftopidil