α-Adrenoceptor blockade and class III antiarrhythmic activity combined: hemodynamic and electrophysiological effects of melperone in the dog

Abstract

Melperone has been found to possess vasodilating and slight positive inotropic properties in addition to its class III antiarrhythmic action. To determine whether some of these effects might be related to an α-adrenoceptor blocking action of melperone, phenoxybenzamine (10 mg/kg) was given as a 2-h infusion to 12 pentobarbital-anesthetized dogs. In addition, six of the dogs were given atenolol 0.5 mg/kg i.v. After a 1-h stabilizing period, melperone (0.5,2.5, and 12.5 mg/kg) was given i. v. in cumulative doses to both series of dogs. In the presence of α-blockade as well as combined α- and β-blockade, atrial, atrioventricular (AV) nodal, and ventricular refractoriness increased and heart rate and AV nodal conduction time decreased, as previously reported after addition of melperone alone. A slight increase in left ventricular (dP/dt)max occurred after the addition of melperone (2.5 mg/kg) in the presence of α- and β-blockade, but only after the highest dose of melperone were small decreases in blood pressure and total peripheral resistance induced. The present study indicates that melperone combines the properties of class III antiarrhythmic action, slight positive inotropy, and α-adrenoceptor mediated vasodilation.