Diphenidol: a new agent for the treatment of digitalis-induced arrhythmias electrophysiologic and hemodynamic studies

Abstract

Diphenidol, a new antiemetic, has been shown to be effective in treating arrhythmias secondary to digitalis intoxication. In a control series of 20 dogs given toxic doses of digoxin, 14 dogs (67 percent) died in 24 hours. In a second group of dogs, given a similar dose of digoxin followed by 0.5 to 4 mg/kg of diphenidol, there was only 1 death ( P < 0.001). His bundle electrograms were recorded in another series of dogs and demonstrated shortening of the A-H time with a maximal decrease (−20 ± 4.7 percent) seen after administration of 0.5 to 4 mg/kg of diphenidol. After administration of toxic doses of ouabain (> 40 μg/kg), diphenidol (0.5 to 4 mg/kg) shortened the prolonged A-H time in these animals (−22.8 ± 5 percent). In contrast, diphenidol diluent alone exerted no significant effect. No change in sinus rate of isolated right atrial preparations was seen until exposure to diphenidol (≥1 × 10 −4 M), when a marked negative chronotropic effect was seen. Diphenidol was also observed to suppress the enhanced ventricular automaticity induced by digitalis. Hemodynamic studies in the intact animal, after administration of 4 mg/kg of diphenidol, demonstrated no significant effect on cardiac index, total peripheral vascular resistance, arterial pressure, stroke volume or coronary flow. In isolated cat papillary muscle diphenidol, in contrast to equimolar doses of propranolol, demonstrated no significant negative inotropic effect until exposure to a level of ≥1 × 10 −5 M. In conclusion, the experimental data demonstrate that diphenidol possesses desirable antiarrhythmic properties especially for the treatment of digitalis-induced arrhythmias.