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

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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 (.gtoreq. 0.25 mg/kg), increases corrected sinus node recovery time, and decreases Wenckebach point (.gtoreq. 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 (.gtoreq. 0.25 mg/kg) and Wenckebach point (.gtoreq. 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.