Cardiovascular responses to increasing plasma concentrations of AQ-A 39 Cl, a new compound with negative chronotropic effects.

5,6-Dimethoxy-2-((3[(alpha-(3,4-dimethoxy) phenylethyl)-methylamino]propyl))-phthalimidine hydrochloride (AQ-A 39 Cl, in the following briefly called AQ-A 39) is a new compound with a structure similar to that of verapamil and which exhibits a specific bradycardic effect by a direct action on the sinus node. In nine anesthetized pigs the compound produced a dose-dependent decrease in heart rate up to 35%. For concentrations less than 1500 ng . ml-1, the drug exerted only minor effects on myocardial contractility (less than 5%), but for concentrations greater than 2000 ng . ml-1 negative inotropic properties became apparent and cardiac output decreased up to 25%, in spite of an increase in stroke volume. Left ventricular filling pressure and systemic vascular resistance were not affected. Myocardial O2-consumption also decreased dose-dependently up to 35%. The reduction in heart rate was not the only factor in determining the magnitude of this decrease as substantial decreases (25-30%) were also observed when, during drug administration, the heart rates were raised to 120 and 150 beats . min-1, respectively by means of coronary sinus pacing. The decrease in myocardial O2-consumption was reflected by decreases in both coronary blood flow and myocardial O2-extraction, while coronary vascular resistance did not change. The cardiovascular profile of AQ-A 39 indicated that, especially for arterial plasma concentrations lower than 1500 ng . ml-1, the drug may be useful in the treatment of tachycardias and in lowering myocardial O2-demand, without adverse effects on cardiovascular performance.