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Titolo:
In vivo canine model comparison of cardiohemodynamic and electrophysiological effects of a new antipsychotic drug aripiprazole (OPC-14597) to haloperidol
Autore:
Sugiyama, A; Satoh, Y; Hashimoto, K;
Indirizzi:
Yamanashi Med Univ, Dept Pharmacol, Yamanashi 4093898, Japan Yamanashi MedUniv Yamanashi Japan 4093898 col, Yamanashi 4093898, Japan
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 2, volume: 173, anno: 2001,
pagine: 120 - 128
SICI:
0041-008X(20010601)173:2<120:IVCMCO>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTION-POTENTIAL DURATION; TORSADE-DE-POINTES; ANTIARRHYTHMIC DRUGS; IN-VIVO; PROKINETIC AGENTS; MAGNESIUM-SULFATE; CRITICALLY ILL; HEART; DOPAMINE; REFRACTORINESS;
Keywords:
aripiprazole; haloperidol; monophasic action potential; long QT syndrome; dopamine autoreceptor agonist; antipsychotic drug; OPC-14597;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Sugiyama, A Yamanashi Med Univ, Dept Pharmacol, Tamaho Cho, Yamanashi 4093898, Japan Yamanashi Med Univ Tamaho Cho Yamanashi Japan 4093898 , Japan
Citazione:
A. Sugiyama et al., "In vivo canine model comparison of cardiohemodynamic and electrophysiological effects of a new antipsychotic drug aripiprazole (OPC-14597) to haloperidol", TOX APPL PH, 173(2), 2001, pp. 120-128

Abstract

The cardiovascular effects of aripiprazole were assessed in comparison with those of haloperidol using a halothane-anesthetized canine model with monophasic action potential monitoring. Aripiprazole (n = 6) or haloperidol (n= 6) was infused over 10 min at escalating doses of 0.03, 0.3, and 3.0 mg/kg with intervals of 20 min between doses. Clinically relevant plasma concentrations were obtained after 0.03-0.3 mg/kg of aripiprazole as well as haloperidol. After 0.03-0.3 mg/kg of aripiprazole, positive chronotropic, inotropic, and dromotropic effects, shortening of the ventricular effective refractory period (ERP) and repolarization phase, and decrease of total peripheral resistance were observed in a dose-related manner. However, in the presence of a beta -blocking dose of esmolol (0.1 mg/kg/min), these changes were not induced. After 3.0 mg/kg of aripiprazole administration, cardiac effects induced by the lower doses were attenuated or disappeared, while the negative chronotropic, dromotropic, and hypotensive actions and prolongationof ERP and repolarization phase were induced. After 0.03 mg/kg of haloperidol, no significant change was observed, except for the decrease of the peripheral resistance. After 0.3-3.0 mg/kg of haloperidol, negative chronotropic, inotropic, and hypotensive actions, intraventricular conduction delay, and prolongation of ventricular ERP and repolarization phase were observed in a dose-related manner accompanied by further decrease of the peripheral resistance. The inhibitory effects of aripiprazole on cardiovascular parameters in dogs were less potent than those of haloperidol at clinically relevant exposures, moreover, aripiprazole, unlike haloperidol, neither induced early afterdepolarization nor prolonged the ventricular electrical vulnerable period. Therefore, aripiprazole can be considered safer to use than haloperidol. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 01:43:20