Pharmacodynamic interaction of gallopamil and propranolol in the conscious dog

The interaction of gallopamil (Procorum) and propranolol was studied in conscious trained dogs by injecting gallopamil intravenously (consecutive injection of 0.0464, 0.1 and 0.215 mg/kg at 30-min intervals) with and without propranolol pre-medication (0.464 mg/kg i.v., 10 min before the first injection of gallopamil). An intraindividual comparison of the cardiovascular effects was made. The interaction was mostly minor and occurred only with the highest dose of gallopamil. It was noticeable most in the influence on myocardial contractility which was more pronounced than the influence on electrophysiological parameters. A shift in threshold doses was not observed. Much more pronounced effects of the gallopamil-propranolol interaction become apparent when the animals were at the same time subjected to vagal blockade (methylatropine). In this situation, combined administration of gallopamil and propranolol led to a greater reduction of contractility, increase of AV block and occurrence of asystole. As regards the latter, a shift in the threshold dose occurred. The differences in the intensity of the interaction between gallopamil and propranolol in animals with or without vagal blockade are therefore a consequence of the presence or absence of reflex regulation. The findings explain, and relativize, the clear-cut interaction in the anaesthetized dog demonstrated by other authors, i.e. experimental conditions matching an autonomic blockade.