Bethanidine sulfate is a closely related chemical analog of
bretylium that has virtually identical pharmacologic and antifibrillatory actions on the ventricle. Unlike
bretylium, which is very poorly absorbed from the gut,
bethanidine is rapidly and effectively absorbed after
oral administration.
Bethanidine increased
ventricular fibrillation threshold in the normal dog heart from an average control value of 28.5 mA to an average peak value of 66.5 mA, an increase of 150 percent. In the infarcted heart,
bethanidine increased
ventricular fibrillation threshold from an average postinfarction level of 14.4 mA to an average peak value of 55.3 mA, an increase of 327 percent. Like
bretylium, the antifibrillatory action of
bethanidine was manifested by the appearance of nonsustained
ventricular fibrillation when superthreshold shocks induced episodes of
ventricular fibrillation lasting from 2 to 120 seconds and converting spontaneously to sinus rhythm. In contrast, the untreated dog heart must always be defibrillated electrically. The onset of antifibrillatory action began as early
as 2 minutes after
intravenous administration and 15 to 30 minutes after
oral administration; peak action occurred in approximately 60 minutes.
Bethanidine had prolonged positive inotropic action in the isolated heart as reflected by an increase in cardiac output and blood pressure lasting up to 60 minutes.
Bethanidine lowered coronary vascular resistance and increased coronary blood flow. The oral efficacy and rapid onset of action gives
bethanidine a potential role in the prevention of out-of-hospital
ventricular fibrillation.