Effect of Chinoin-103, a new antiarrhythmic drug, on the transmembrane potentials, ionic currents and contractile force in heart muscle

J. Meszaros, K. Kelemen, R. Marko, V. Kecskeméti, D. Korbonits, G. Kovács, J. Szegi

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Abstract

The effect of Chinoin-103 (CH-103) was examined on the electrophysiological and mechanical properties of the isolated guinea-pig atrial and ventricular myocardium and on membrane ionic currents of the frog atrial trabeculae using glass-microelectrode and voltage clamp techniques. In the guinea-pig atrial and ventricular myocardium, CH-103 had no effect on the resting membrane potential, but decreased the action potential overshoot and maximum rate of depolarization (V̇(max)). CH-103 exerted a negative inotropic effect on both preparations. The drug (10-5 M) consistently shifted the membrane responsiveness curve to more negative potentials. CH-103 rapidly abolished the membrane electrogenesis in myocardial preparations pretreated with 5 mM MnCl2. The slow action potentials induced in K+-depolarized preparations by caffeine were slightly reduced, whereas the isoproterenol-induced ones were markedly depressed by the drug. In voltage clamp experiments, CH-103 strongly reduced the fast inward Na+ current, but hardly decreased the slow inward Ca2+ current and the delayed outward K+ current. These results suggest that CH-103 has both membrane stabilizing and beta-blocking effects, and can explain the antiarrhythmic action of CH-103.

Original languageEnglish
Pages (from-to)250-267
Number of pages18
JournalArchives internationales de pharmacodynamie et de therapie
Volume262
Issue number2
Publication statusPublished - Jun 10 1983

ASJC Scopus subject areas

  • Pharmacology

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