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.
Vaughan Williams
E M
EM
Hartford College, Oxford University.
D000200:Action Potentials / Q000187:drug effects; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D004562:Electrocardiography / Q000187:drug effects*; D004594:Electrophysiology; D006801:Humans; D016293:Moricizine / Q000145:classification* / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D016293:Moricizine