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- W2280645293 abstract "We compared the electrophysiologic, inotropic and antiarrhythmic properties of propafenone and two metabolites, 5-hydroxy (5-OH) propafenone and N-depropyl (N-DP) propafenone. In 18 canine Purkinje fibers with normal maximum diastolic potentials, all drugs (1 x 10(-8) to 1 x 10(-5) M) reduced action potential amplitude and duration. However, propafenone and 5-OH propafenone reduced Vmax in a use-dependent fashion at a lower concentration than N-DP propafenone. In 16 Purkinje fibers, slow response action potentials were induced by 22 mM K+ and isoproterenol, 1 x 10(-6) M. Vmax was comparably reduced by all compounds at 1 x 10(-5) M, but action potential amplitude was not affected by 5-OH propafenone. In 16 other Purkinje fibers in which automaticity at low levels of membrane potential was induced by BaCl2 (0.25 mM), only 5-OH propafenone was effective in slowing the automatic rate at therapeutic concentrations (3 micrograms/ml). In 15 guinea pig papillary muscles, all three drugs had negative inotropic effects at concentrations greater than or equal to 1 x 10(-6) M. In conscious dogs with sustained ventricular tachycardia 24 hr after infarction, we injected propafenone or a metabolite through an atrial cannula. At similar plasma levels, neither propafenone (n = 6) nor N-DP propafenone (n = 6) suppressed the arrhythmia, whereas 5-OH propafenone eliminated ventricular tachycardia in four of six dogs, and was more effective against monomorphic than polymorphic ventricular tachycardia. Hence, the two major metabolites of propafenone have important electrophysiologic effects, and 5-OH propafenone is more potent than the parent compound as a antiarrhythmic drug in the 24-hr Harris dog." @default.
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- W2280645293 date "1988-08-01" @default.
- W2280645293 modified "2023-09-27" @default.
- W2280645293 title "Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone." @default.
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