UNIQUENESS OF PILSICAINIDE IN CLASS IC ANTIARRHYTHMICS

Pilsicainide, a class Ic agent, is known to be an effective drug parti cularly for treating atrial tachyarrhythmias. However, its electrophys iological effects on the atrium have not been well studied. To charact erize the electrophysiologic effects of pilsicainide on atrial myocyte s in class Ic drugs, we examined the effects of this drug on membrane currents in single rabbit atrial myocytes using the tight-seal whole c ell voltage-clamp technique. Under the current-clamp condition, pilsic ainide did not affect the action potential duration at therapeutic ran ges (less than or equal to 3 mu M) and slightly shortened it at higher concentrations (greater than or equal to 10 mu M). These observations were quite different from those with other class Ic agents including flecainide and propafenone which prolong the atrial action potential d uration. The drug did not affect the resting membrane potential. Under the voltage-clamp condition, pilsicainide inhibited the transient out ward current (I-to) that is more prominent in the atrium than in the v entricle in a concentration-dependent manner. However, in contrast to other class Ic agents, the inhibition of I-to by pilsicainide was obse rved only at much higher concentrations (IC(50)similar to 300 mu M) an d did not affect the inactivation time-course of I,. Moreover, the dru g (10 mu M) did not significantly affect the Ca2+, delayed rectifier K +, inward rectifying K+, acetylcholine-induced K+ or ATP-sensitive Kcurrents. From these results, pilsicainide could be differentiated as a pure Na+ channel blocker from other class Ic agents with diverse eff ects on membrane currents and should be recognized accordingly in clin ical situations.