The electrophysiological effects of
bethanidine and
meobentine were studied on isolated canine cardiac tissues and the in situ dog heart using standard techniques. The "direct" electrophysiological effects of
bethanidine (in the beta-
adrenergic-blocked Purkinje fiber) resemble the effects of
meobentine in the normal canine Purkinje fiber; both drugs produce use-dependent decreases of the maximum rate of depolarization of phase 0 and action potential amplitude. In addition,
meobentine prolongs action potential duration (100%) of Purkinje fibers. In ventricular muscle cells, the only significant effect of
meobentine is a decrease in the maximum rate of depolarization. In studies of
ouabain-induced
tachycardias and 24-h
infarct-induced ventricular arrhythmias,
bethanidine tends to increase heart rate and/or exacerbate the ectopic activity (due to its
sympathomimetic effects), whereas
meobentine tends to reduce heart rate and restore normal sinus rhythm. Both
bethanidine and
meobentine increase
ventricular fibrillation threshold. This increase is evident following
bethanidine injection after the subsidence of the
sympathomimetic effects. Finally, moderate increases of
ventricular fibrillation threshold following treatment with
meobentine are accompanied by partial cardiac sympathetic blockade, as indicated by reduced chronotropic responses to stellate ganglion stimulation. The antiarrhythmic and antifibrillatory effects of
bethanidine and
meobentine may be explained by the use-dependent effects of these drugs on phase 0 of the action potential and by their
sympatholytic actions on the autonomic nervous system.
Meobentine may, in addition, exert antiarrhythmic effects by decreasing automaticity in partially depolarized cells.