MORACIZINE HYDROCHLORIDE

Description

Moricizine hydrochloride is a phenothiazine derivative with antiarrhythmic activity developed by the Soviet Academy of Medical Sciences. It is licensed to Dupont-Sanko in a joint venture. Moricizine hydrochloride is the first drug licensed to a U.S. company by the Soviet Union and was introduced by Dupont in the U.S. in 1990 for specific use in Iife-threatening ventricular arrhythmias. This narrow indication reflects its proarrhythmic potential. The incidence of this adverse reaction, however, is lower than that of other antiarrhythmic agents.

Originator

Acad. Med. Sci. (USSR)

Uses

Moricizine Hydrochloride is a Phenothiazine (P318040) derivative, which It was used as an antiarrhythmic agent. It is also shown that moracizine is effective in suppressing premature ventricular contractions, couplets, and nonsustained ventricular tachycardia.

Uses

Cardiac depressant (anti-arrhythmic).

Definition

ChEBI: A hydrochloride salt obtained from equimola amounts of moricizine and hydrogen chloride.

Manufacturing Process

To a solution of 10 g (0.035 mole) of ethyl phenthiazine-2-carbamate in 30 ml of anhydrous toluene is added dropwise 5.3 g (0.042 mole) of 3- chloropropionyl chloride, and the mixture is refluxed at 110-120°C for 4 hours, followed by clarifying the mixture with activated carbon and cooling it to room temperature. A precipitate of ethyl 10-(3-chloropropionyl)- phenthiazine-2-carbamate is removed by filtration. The yield is 10.2 g (77.5% of the theoretical amount), M.P. 169-170°C.
10.2 g of ethyl 10-(3-chloropropionyl)-phenthiazine-2-carbamate ester is dissolved in 50 ml of toluene, 4.72 g of morpholine is added thereto, and the mixture is refluxed at 110-120°C for a period of 3 hours. A precipitate of morpholine hydrochloride is removed by filtration, and the filtrate is washed with water in order to remove excess morpholine, followed by acidulating with dilute hydrochloric acid to adjust the pH of the filtrate is adjusted at 3. The acidic aqueous layer is separated, clarified by treatment with activated carbon and made alkaline until the pH equals 8-9. This procedure yields the free base of ethyl 10-(β-morpholylpropionyl)-phenthiazine-2-carbamate, M.P. 156- 157°C.
The free base thus obtained is extracted with toluene, the extract is dried over magnesium sulphate and to the anhydrous toluene solution is added an anhydrous ethereal solution of hydrogen chloride until the precipitation of the target compound is complete. This procedure yields 9.53 g (76.2% of the theoretical amount) of ethyl 10-(β-morpholylpropionyl)-phenthiazine-2- carbamate hydrochloride. After recrystallization from dichloroethane, the target compound melts at 189°C. (decomp.).

brand name

Ethmozine (Shire).

Therapeutic Function

Antiarrhythmic