New classification of moricizine and propafenone based on electrophysiologic and electrocardiographic data from isolated rabbit heart.

Because the classification of propafenone and moricizine is not clear, we measured in 20 specifically equipped isolated rabbit hearts QRS duration, QT interval, action potential duration at 90% of repolarization (APD90), effective refractory period (ERP), conduction time (CT), and rise velocity (Rv) of the monophasic action potentials (AP) during exposure to moricizine and propafenone in comparison with procainamide. Propafenone and procainamide prolonged APD90 and JT. All drugs increased ERP. Propafenone demonstrated marked tonic sodium channel block. Onset of use-dependent kinetics (tau on), defined as change in Rv as fraction per beat at 300 ms cycle length (CL), were 0.047 +/- 0.004/beat for procainamide, 0.050 +/- 0.004/beat for propafenone, and 0.022 +/- 0.003/beat for miricizine. Recovery kinetics, defined as recovery of Rv after cessation of pacing, had a time constant of 5.3 +/- 0.7 s for procainamide, 6.3 +/- 0.8 s for propafenone, and 25.0 +/- 1.3 s for moricizine. Based on these data, moricizine must be classified as a Ic agent, whereas propafenone demonstrates pronounced tonic sodium channel block, in addition to its phasic block, which is similar to class Ia kinetics.

Classification of the antiarrhythmic action of moricizine.

The subdivisiion of class 1 antiarrhythmic agents into groups a, b, and c was originally based on clinical electrophysiologic findings. Class 1b compounds did not alter QRS or HV interval in sinus rhythm, but the compounds did lengthen ERP in spite of shortening JT. Class 1c agents widened QRS and prolonged HV at low concentrations in sinus rhythm, but had little effect on ERP or JT. Cellular electrophysiologic studies provided an explanation for these clinical effects by frequency-dependent onset/offset kinetics. Class 1b drugs became rapidly attached to sodium channels after depolarization, which rendered them nonconducting, but the drugs also dissociated rapidly after repolarization so that by the end of a normal diastole nearly all channels were back to their conducting state. In contrast, class 1c drugs became more slowly attached, and more slowly detached, so that a proportion of sodium channels was permanently eliminated as long as the drug was present. This caused slow conduction in the His-Purkinje system and ventricle. Both clinical and cellular electrophysiologic studies show that moricizine HCl is a class 1c agent.