Electrophysiological effects of amperozide in papillary muscles from ferrets, guinea-pigs and rabbits

Amperozide, a novel psychotropic agent, in concentrations lower than 10 microM caused a homogenous prolongation only of the action potential in both guinea-pig and rabbit papillary muscle. In concentrations greater than or equal to 10 microM, amperozide caused a flattening of the action potential plateau and the later part of the repolarization phase became slower (longer), probably reflecting an impaired repolarizing Na-Ca exchange current. The overshoot (OS) and the rate of rise of the action potential (dV/dtmax) were depressed. It is concluded that amperozide has a blocking action on the transmembrane calcium current since Isi (second inward current), DIA (depolarization induced automaticity) and the peak force of contraction were depressed. The blocking of the Isi was use-dependent resembling the actions of calcium-antagonists like verapamil, except that it was less potent at equimolar concentrations. Amperozide in concentrations where it acted as an Isi-blocker (above 10 microM), had depressing effects only on ouabain-induced oscillatory events. No major differences in the effects of amperozide were apparent between guinea-pig, ferret or rabbit papillary muscles.