title: Naftopidil inhibits 5-hydroxytryptamine-induced platelet aggregation and 5-hydroxytryptamine uptake in platelets of healthy volunteers.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, University of Frankfurt, Main, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kirsten
authors.forename: M
authors.initials: M
authors.lastname: Breidert
authors.forename: K
authors.initials: K
authors.lastname: Nelson
authors.forename: A
authors.initials: A
authors.lastname: Heine
authors.forename: S
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: B
authors.initials: B
authors.lastname: Erdeg
authors.forename: G
authors.initials: G
authors.lastname: Niebch
authors.forename: H O
authors.initials: HO
authors.lastname: Borbe
authors.forename: M
authors.initials: M
authors.lastname: Siebert-Weigel
authors.forename: J
authors.initials: J
authors.lastname: Respondek
mesh_terms: 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*
chemical_list: D002121:Calcium Channel Blockers; D009281:Naphthalenes; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C064357:naftopidil