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 It was used for the prophylaxis and treatment of serious and life-threatening ventricular arrhythmias, but was withdrawn in 2007 for commercial reasons.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 Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. ...

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 at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

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 b ...

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 is classified as a Class 1a anti-arrhythmic agent. Disopyramide has a neg ...

and

quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is a diastereomer 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 contraction A premature ventricular contraction (PVC) is a common event where the heartbeat is initiated by Purkinje fibers in the ventricles rather than by the sinoatrial node. PVCs may cause no symptoms or may be perceived as a "skipped beat" or felt as ...

s, couplets, and nonsustained

ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple ...

. 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 contraction, premature ventricular complexes (PVC) with class I antiarrhythmi ...

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

The reaction between N-phenyl-1,3-benzenediamine (1) and

ethyl chloroformate Ethyl chloroformate is an organic compound with the chemical formula . It is the ethyl ester of chloroformic acid. It is a colorless, corrosive and highly toxic liquid. It is a reagent used in organic synthesis for the introduction of the ethyl c ...

(2) gives the

carbamate In organic chemistry, a carbamate is a category of organic compounds with the general Chemical formula, formula and Chemical structure, structure , which are formally Derivative (chemistry), derived from carbamic acid (). The term includes orga ...

(3). Treatment with sulfur and iodine forms the phenothiazine derivative (4).

Amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

formation with 3-chloropropionyl chloride (5) gives the penultimate intermediate (6).

Alkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

morpholine Morpholine is an Organic compound, organic chemical compound having the chemical formula oxygen, O(carbon, Chydrogen, H2CH2)2nitrogen, NH. This heterocycle features both amine and ether functional groups. Because of the amine, morpholine is a bas ...

nucleophilic substitution In chemistry, a nucleophilic substitution (SN) is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile) ...

at the sidechain chlorine yields moricizine.

References

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