Moracizine or moricizine, sold under the trade name Ethmozine, is an antiarrhythmic of class IC. It was used for the prophylaxis and treatment of serious and life-threatening ventricular arrhythmias, but was withdrawn in 2007 for commercial reasons.

Pharmacology

Moracizine, a phenothiazine derivative, undergoes extensive

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemi ...

and is also extensively metabolized after it has entered the circulation. It may have pharmacologically active metabolites. A clinical study has shown that moracizine is slightly less effective than

encainide Encainide (trade name Enkaid) is a class Ic antiarrhythmic agent. It is no longer used because of its frequent proarrhythmic side effects. Synthesis See also * Iferanserin * Cardiac Arrhythmia Suppression Trial The Cardiac Arrhythmia Suppr ...

flecainide Flecainide is a medication used to prevent and treat abnormally fast heart rates. This includes ventricular and supraventricular tachycardias. Its use is only recommended in those with dangerous arrhythmias or when significant symptoms cannot ...

in suppressing ventricular premature depolarizations. Compared with

disopyramide Disopyramide ( INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication used in the treatment of ventricular tachycardia. It is a sodium channel blocker and therefore classified as a Class 1a anti-arrhythmic agent. Disopyramide has ...

and

quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

, moracizine was equally or more effective in suppressing premature ventricular contractions, couplets, and nonsustained

ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period ...

. In the

Cardiac Arrhythmia Suppression Trial The Cardiac Arrhythmia Suppression Trial (CAST) was a double-blind, randomized, controlled study designed to test the hypothesis that suppression of premature ventricular complexes (PVC) with class I antiarrhythmic agents after a myocardial infarc ...

(CAST), a large study testing the influence of antiarrhythmics on

mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

, showed a statistically non-significant increase of mortality from 5.4 to 7.2% under moracizine. This is in line with other class IC antiarrhythmics.

Synthesis

Note: The carbamate structure reminds the reader o
Gastrophenzine
or particularly

Ethacizine Ethacizine (ethacyzine) is a class Ic antiarrhythmic agent, related to moracizine. It is used in Russia and some other CIS countries for the treatment of severe and/or refractory ventricular and supraventricular arrhythmias, especially those acc ...

The amide formation between Phenothiazine-2-ethylcarbamate 7711-29-8(1) and 3-Chloropropionyl chloride 25-36-5(2) gives ethyl N- 0-(3-chloropropanoyl)phenothiazin-2-ylarbamate 19407-03-3 4749-22-9(3). Displacement of the remaining ω-halogen by

morpholine Morpholine is an organic chemical compound having the chemical formula O( C H2CH2)2 NH. This heterocycle features both amine and ether functional groups. Because of the amine, morpholine is a base; its conjugate acid is called morpholinium. Fo ...

(4) then completes the synthesis of Moricizine (5).

References

Antiarrhythmic agents Sodium channel blockers Phenothiazines 4-Morpholinyl compunds Carbamates Abandoned drugs Drugs in the Soviet Union {{cardiovascular-drug-stub