B-GYKI-38233

The effect of restacorin and flecainide on the early afterdepolarization (EAD) and on the delayed afterdepolarization (DAD) was studied in dog cardiac Purkinje fibers by applying the conventional microelectrode technique. Restacorin and flecainide at 5 microM concentration partially abolished EAD. Further increase of the concentrations of the drugs to 10 microM EADs were completely abolished. The amplitude of DADs were significantly decreased by both restacorin (9.9 +/- 2.1 mV v.s. 2.9 +/- 1.8 mV, p < 0.01, n = 5) and flecainide (11.1 +/- 1.3 mV v.s. 0.6 +/- 0.6 mV, p < 0.01, n = 7). These results suggest that the well-established antiarrhythmic effect of restacorin and flecainide at least partially may be explained by their beneficial action against triggered abnormal automaticity.

The effect of restacorin (5 microM) and flecainide (5 microM) on the transmembrane ionic currents was compared in dog and rabbit ventricular muscle by applying the conventional microelectrode and patch-clamp techniques. Neither restacorin nor flecainide influenced significantly the ATP-sensitive and inward rectifier potassium currents. Flecainide moderately decreased the amplitude of the transient outward current while restacorin did not change this current. The delayed rectifier potassium current was depressed markedly by flecainide and moderately by restacorin. These results suggest that although flecainide and restacorin cause similar changes in the various transmembrane ionic currents, there are some differences between the effects of the two antiarrhythmic compounds.