Action of dimethindene on the electrophysiological and mechanical properties of atrial and ventricular myocardium of guinea-pig

Abstract

The effect of dimethindene (DMI) on transmembrane potentials and contractile force was studied in atrial and ventricular myocardium of guinea-pigs. DMI reduced the maximum rate of depolarization (V̇ max) without changing the resting potential in both preparations. In ventricular myocardium, DMI shortened the action potential duration and exerted a negative inotropic effect. In atrial muscle, the drug prolonged the action potential duration and induced a positive inotropic effect which could be antogonized with neither the α-blocker phentolamine, nor the β-blocker pindolol, H 1-blocker mepyramine and H 2-blocker cimetidine. DMI had no effect on the slow action potentials induced by caffeine in K +-depolarized myocardial preparations. The drug consistently shifted the sodium inactivation curve to more negative membrane potentials. The results suggest that DMI has a quinidine-like membrane-stabilizing property, which may be due to its fast Na + channel blocking activity. The differential inotropic action of the drug in atrial and ventricular myocardium is discussed.