Moricizine: A Novel Antiarrhythmic Agent

Abstract

Moricizine is a phenothiazine derivative with Vaughan Williams class 1 antiarrhythmic properties. It undergoes extensive first-pass metabolism, has a bioavailability of 34-38 percent, and is 95 percent bound to plasma proteins. Moricizine is extensively metabolized and may have pharmacologically active metabolites. A recent clinical study has shown that moricizine is slightly less effective than encainide or flecainide in suppressing ventricular premature depolarizations. Compared with disopyramide and quinidine, moricizine was equally or more effective in suppressing ventricular premature depolarizations, couplets, and nonsustained ventricular tachycardia. Further studies are needed comparing moricizine with other class 1 agents in the treatment of life-threatening arrhythmias; available data suggest that moricizine is comparable with these agents in the treatment of ventricular tachycardias and fibrillation. Moricizine appears to have a low incidence of serious adverse effects compared with other antiarrhythmics. This combination of apparently similar efficacy with a decreased incidence of adverse effects makes moricizine a worthwhile addition to currently available antiarrhythmic agents.

Moricizine Hydrochloride: Pharmacology, Pharmacokinetics, and Clinical Studies

“…The drugs studied include digoxin, cimetidine, warfarin, propranolol, and theophylline. Combined use of moricizine HC1 and digoxin may result in a slightly greater increase in the PR interval than would be expected with either drug alone, but no statistically or clinically significant alterations of either drug have been noted (9). Simultaneous use of moricizine HCl and cimetidine reveals increased elimination half life and plasma concentration of moricizine (6).…”

“…Furthermore, the bioavailability of moricizine tablets and oral solution has been found to be the same (30). The relatively rapid absorption and comparable bioavailability of the oral dosage forms suggest that moricizine is well absorbed (9).…”

“…Plasma protein binding to albumin and alpha,-acid glycoprotein is about 95% (9). The volume of distribution is about 225 liters (approximately 4 liters/kg) (9). These pharmacokinetics imply significant peripheral tissue binding.…”

“…Moricizine HC1 has activities similar to the Class IB agents in that it displays an increased rate of phase 2 and phase 3 repolarization (16,29,50). In isolated canine h r kinje fibers, moricizine HCl shortened the APD to a greater extent than the effective refractory period, resulting in an increased ratio of the effective refractory period to the duration of the action potential (9,10,16). This may be a contributing factor to the drug's antiarrhythmic effect.…”

“…The electrophysiological effects of moricizine have been studied in various isolated cardiac cells of human, dog, frog, guinea pig, and rat. Like other Class IA agents, moricizine HCl reduces transmembrane sodium channel conductance, inhibiting the fast influx of Na+ responsible for phase 0 depolarization (8)(9)(10)34,50), and reducing the maximal upstroke of phase 0 of the transmembrane action potential. Moricizine HCl may bind to sodium channels in the resting, open, or inactivated states (5).…”