We examined the effects of nicainoprol (1-50 microM), a new antiarrhythmic agent, on the transmembrane action potentials in isolated papillary muscles of the guinea pig. Nicainoprol (greater than or equal to 5 microM) produced dose-dependent decreases in the maximal upstroke velocity (Vmax) of the action potential. Only the highest concentration (50 microM) decreased the amplitude and the overshoot of the action potential and shortened its duration at 50 or 90% repolarization levels (APD50, APD90). The potential at rest was not affected by any concentration tested (1-50 microM). In the presence of nicainoprol, trains of stimuli at the rate of 0.2, 0.5, 1.0, and 2.0 Hz, introduced after a sufficient period of rest, led to an exponential decay of the Vmax to the steady state levels (use-dependent block, UDB). The UDB was augmented with an increase in the stimulation frequency or with a decrease in the potentials at rest. The time constant for the recovery from the UDB was 51.6 +/- 9.4 s at 50 microM. The Vmax and the amplitude of the slow response elicited in the presence of 27 mM [K+]o and 0.2 mM Ba2+ was significantly decreased by application of nicainoprol (10-100 microM), with a significant shortening of APD50 (100 microM). These findings suggest that nicainoprol has electrophysiologic properties in common with those of other class I antiarrhythmic drugs with slow kinetics (Ic) and has a minor but significant inhibitory effect on slow inward current (class IV effect).