Effects of
SUN 1165,
disopyramide,
lorcainide, and
mexiletine were studied either on the kinetics of onset of and recovery from rate-dependent depression of maximum rate of rise of phase 0 action potential (Vmax) in isolated guinea pig papillary muscles using standard
microelectrode techniques or on intraventricular conduction time of
extrasystoles evoked at varied coupling intervals in anesthetized dogs.
SUN 1165 and
lorcainide produced a slow-developing rate-dependent block of Vmax with the rate constant of 0.12
AP-1 and 0.09
AP-1, respectively.
Mexiletine also produced a rate-dependent block of Vmax, but with very rapid onset so as not to be fitted by a single exponential curve.
Disopyramide produced an intermediate rate-dependent block of Vmax with the rate constant of 0.46
AP-1. The time constants for recovery from the rate-dependent block for
SUN 1165,
lorcainide and
disopyramide were 27.3-28.2, 23.2, and 17.0 s, respectively, while that for
mexiletine was 0.118 s.
SUN 1165,
lorcainide, and
disopyramide slowed ventricular conduction time of
extrasystoles at all coupling intervals of 800-250 ms. On the other hand,
mexiletine slowed conduction time at short coupling intervals of 500-250 ms. These findings suggest that, like
lorcainide,
SUN 1165 belongs to class Ic antiarrhythmic agents, and that
SUN 1165 and
lorcainide as well as
disopyramide with slow and intermediate kinetics and
mexiletine with fast kinetics may inhibit
ventricular extrasystoles conducted at long and short range of coupling intervals, respectively.