Electrophysiological effects of 711389-S, a new antiarrhythmic agent, on guinea-pig isolated cardiac muscle.

The effects of 711389-S, a newly developed antiarrhythmic agent, on transmembrane action potentials were examined in isolated papillary muscles of guinea pigs. 711389-S above 10(-6) M caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) and a slight prolongation of the action potential duration (APD) at a late repolarization phase. The resting potential, the amplitude, and APD at an early repolarization phase were not affected even at 10(-5) M. In the presence of 711389-S, trains of stimuli higher than 0.1 Hz led to an exponential decline in Vmax to a new plateau level. This use-dependent block was augmented at the higher stimulation frequency. The time constant for the recovery from the use-dependent block was 47 s at 3 X 10(-6) M. At 1.0 Hz, 711389-S caused an appreciable shift (6.8 mV) of the curve relating the membrane potential and Vmax along the voltage axis in the hyperpolarizing direction, but no shift at 0.1 Hz. The antagonistic effect of 711389-S against acetylcholine in guinea-pig isolated atria was much less than that of disopyramide. These findings suggest that 711389-S has similar electrophysiological effects to those of other Class Ia antiarrhythmic drugs but has much less anticholinergic activity.