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  • Title: Cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in the conscious dog.
    Author: Boucher M, Chassaing C, Hamel JD, Poirier JM.
    Journal: Eur J Pharmacol; 1996 Nov 14; 315(2):171-7. PubMed ID: 8960881.
    Abstract:
    We studied the cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in conscious dogs. Sinus rate, corrected sinus recovery time and Wenckebach point were measured in 6 intact dogs. Atrial rate, ventricular rate and atrial effective refractory period were measured in 6 atrioventricular-blocked dogs. In both groups, we also determined blood pressure and plasma drug concentrations. Each dog received, with at least an 8-day interval, propafenone (hydrochloride) and 5-hydroxypropafenone (hydrochloride) in 4 successive intravenous injections, 30 min apart, at 0.5, 0.5, 1 and 2 mg kg(-1). Propafenone increased sinus rate and atrial rate more markedly than 5-hydroxypropafenone, and also transiently ventricular rate, whereas 5-hydroxypropafenone decreased it weakly. Propafenone shortened corrected sinus recovery time and increased Wenckebach point at the highest dose only, whereas 5-hydroxypropafenone did not modify corrected sinus recovery time and increased Wenckebach point less markedly than propafenone. Both drugs produced an identical atrial effective refractory period lengthening. Propafenone either increased mean blood pressure (in intact dogs) or decreased it (in atrioventricular-blocked dogs) at the highest dose only, whereas 5-hydroxypropafenone did not produce any effect on this parameter. Overall, these results show that propafenone and 5-hydroxypropafenone exhibit cardiac electrophysiological effects, reflecting (a) direct vagolytic action for both drugs associated with cardiodepressant effects for 5-hydroxypropafenone, and (b) marked atrial antiarrhythmic properties for 5-hydroxypropafenone probably involved in the therapeutic effect of propafenone.
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