Effects of Diproteverine, a New Calcium Antagonist on Sinoatrial Node and Atrioventricular Conduction in Conscious Unsedated Dogs

Abstract

The electrophysiologic effects of diproteverine were studied in the conscious nonsedated chronically instrumented dog. Diproteverine at 0.25-0.75 mg/kg (i.e., at plasma levels within the assumed therapeutic range) dose-relatedly decreases heart rate, increases corrected sinus node recovery time, and decreases Wenckebach point. These effects are observed at plasma levels ranging between 16.2 +/- 4.1 and 144.7 +/- 12.5 ng/ml. After cholinergic blockade with N-methylscopolammonium, diproteverine lowers heart rate (greater than or equal to 0.25 mg/kg), increases corrected sinus node recovery time, and decreases Wenckebach point (greater than or equal to 0.5 mg/kg). After propranolol, diproteverine only significantly reduces corrected sinus node recovery time 5 min after the third administration (0.75 mg/kg). After pharmacologic autonomic blockade by N-methylscopolammonium propranolol combination, diproteverine lowers intrinsic heart rate (greater than or equal to 0.25 mg/kg) and Wenckebach point (greater than or equal to 0.5 mg/kg). Diproteverine does not modify mean blood pressure. These results show that diproteverine administered with and without pharmacologic autonomic blockade in the conscious dog causes dose-related depressant effects on sinus node function and atrioventricular conduction without producing significant vasodilatation.