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Titolo:
ANTIARRHYTHMIC EFFECTS OF OPTICAL ISOMERS OF DISOPYRAMIDE ON CANINE VENTRICULAR ARRHYTHMIAS
Autore:
NAKAMURA M; XUE Y; ETO K; HASHIMOTO K;
Indirizzi:
YAMANASHI MED UNIV,DEPT PHARMACOL,TAMAHO CHO YAMANASHI 40938 JAPAN
Titolo Testata:
Journal of cardiovascular pharmacology
fascicolo: 3, volume: 27, anno: 1996,
pagine: 368 - 375
SICI:
0160-2446(1996)27:3<368:AEOOIO>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARDIAC PURKINJE-FIBERS; ELECTROPHYSIOLOGICAL CHARACTERISTICS; PACEMAKER ACTIVITY; R-DISOPYRAMIDE; S-DISOPYRAMIDE; ENANTIOMERS; DRUGS; QUINIDINE; RECEPTOR; METABOLITE;
Keywords:
D-DISOPYRAMIDE; L-DISOPYRAMIDE; VENTRICULAR ARRHYTHMIA; NA CHANNEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
M. Nakamura et al., "ANTIARRHYTHMIC EFFECTS OF OPTICAL ISOMERS OF DISOPYRAMIDE ON CANINE VENTRICULAR ARRHYTHMIAS", Journal of cardiovascular pharmacology, 27(3), 1996, pp. 368-375

Abstract

Disopyramide is an effective class I antiarrhythmic drug and widely used for the treatment of arrhythmias, but it has anticholinergic side effects. In vitro studies demonstrated that dextrorotatory (D-) disopyramide has a stronger anticholinergic action, whereas the levorotatory(L-) isomer has a stronger Na channel blocking action. Because the antiarrhythmic mechanism of disopyramide suppressing digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmias is the drug-induced Na channel block, we examined the antiarrhythmic efficacyof D- and L-disopyramide on two arrhythmia models. On ouabain-inducedventricular tachycardia (VT), L-disopyramide 3 mg/kg decreased the arrhythmic ratio (number of ectopic beats/total heart rate), whereas thesame dose of the D-isomer was ineffective and a higher dose (5 mg/kg)was needed to suppress the arrhythmia. The effective plasma concentrations (IC50) decreasing the arrhythmic ratio to 50% of the control were 5.3 and 11.3 mu g/ml for L- and D-disopyramide, respectively. We obtained similar results using 24-h two-stage coronary ligation VT. The IC50 were 8.9 and 22.2 mu g/ml for the L- and D-isomers, respectively. Our results indicate that L-disopyramide is about twice as strong an antiarrhythmic drug as the D-isomer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 11:11:50