Electrophysiological studies on effects of AQ-A 39 in the isolated guinea pig heart and myocardial preparations.

An isolated perfused hearts as well as in papillary muscles and in Purkinje fibres, the influence of 5,6-dimethoxy-2(3[alpha-(3,4-dimethoxy)phenylethyl)-methylamino]propyl)phthalimidine hydrochloride (AQ-A 39) on the electrical activity was examined (concentration range of AQ-A 39 2.15--10.7 x 10-(5) mol/l). In the isolated heart AQ-A 39 (2.15 x 10(-5) mol/l) reduced the sinus frequency by about 50%. Higher concentrations (up to 10.7 x 10(-5) mol/l) exerted only little additional influence. Similar effects of AQ-A 39 were observed in Ba2+ induced pacemakers in the ventricular myocardium. In Purkinje fibres (K+e 2.7 x 10(-3) mol/l) AQ-A 39 (2.15 x 10(-5) mol/l) reduced the rate of spontaneous discharge to a considerable extent. In papillary muscles as well as in Purkinje fibres the terminal phase of repolarization of the action potential was markedly prolonged without a detectable influence on the resting potential or the maximal rate of rise (Vmax). In the Ba2+ treated depolarized myocardium Vmax was considerably reduced by AQ-A 39. The effects of AQ-A 39 are discussed in view of their ionic mechanisms as well as of the therapeutic application of the drug.