The electrophysiological effects of antiarrhythmic potential of a secoaporphine, N-allylsecoboldine.

1. A satisfactory antiarrhythmic potential of N-allylsecoboldine, a synthetic derivative of secoaporphine, has been documented. Its effects on the ionic currents of cardiac myocytes and the influence on the electrophysiological properties of the conduction system in Langendorff perfused hearts were investigated. 2. Ionic currents were studied by voltage clamp in the whole cell configuration. N-allylsecoboldine blocked the Na channel with a leftward-shift of its half voltage-dependent inactivation and a slower rate of recovery from the inactivation state. Similarly, calcium inward currents were inhibited but to a much smaller extent. 3. N-allylsecoboldine inhibited the 4-AP-sensitive transient outward K current. Currents through the K1 channels were also reduced. 4. As compared with quinidine, N-allylsecoboldine caused a comparable degree of block on Na and K1 currents but blocked to a lesser extent the Ca and Ito currents. 5. In the perfused whole-heart model, N-allylsecoboldine caused a dose-dependent prolongation in sinoatrial, atrioventricular and His-Purkinje system conduction intervals and prolonged the effective refractory periods of the atrium, AV node, His-Purkinje system and ventricle. However, the basic cycle length was not significantly affected. As compared to quinidine, N-allylsecoboldine exerted less pronounced effects on both the basic cycle length and the atrial and AV nodal refractory periods. 6. We conclude that N-allylsecoboldine predominantly blocks Na and K1 channels and in similar concentrations partly blocks Ca channels and Ito. These effects result in a modification of the electrophysiological properties of the conduction system which provides a satisfactory therapeutic potential for the treatment of cardiac arrhythmias.