Moracizine Explained

Moracizine[1] or moricizine, sold under the trade name Ethmozine, is an antiarrhythmic of class IC.[2] It was used for the prophylaxis and treatment of serious and life-threatening ventricular arrhythmias,[3] but was withdrawn in 2007 for commercial reasons.[4]

Pharmacology

Moracizine, a phenothiazine derivative, undergoes extensive first-pass metabolism 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 or flecainide in suppressing ventricular premature depolarizations. Compared with disopyramide and quinidine, moracizine was equally or more effective in suppressing premature ventricular contractions, couplets, and nonsustained ventricular tachycardia.

In the Cardiac Arrhythmia Suppression Trial (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.[5]

Synthesis

The reaction between N-phenyl-1,3-benzenediamine (1) and ethyl chloroformate (2) gives the carbamate (3). Treatment with sulfur and iodine forms the phenothiazine derivative (4). Amide formation with 3-chloropropionyl chloride (5) gives the penultimate intermediate (6). Alkylation of morpholine by nucleophilic substitution at the sidechain chlorine yields moricizine.[6] [7]

See also

Notes and References

  1. Web site: The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. 2009. World Health Organization. 103.
  2. Ahmmed GU, Hisatome I, Kurata Y, Makita N, Tanaka Y, Tanaka H, Okamura T, Sonoyama K, Furuse Y, Kato M, Yamamoto Y, Ogura K, Shimoyama M, Miake J, Sasaki N, Ogino K, Igawa O, Yoshida A, Shigemasa C . Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block . Vascular Pharmacology . 38 . 3 . 131–41 . March 2002 . 12402511 . 10.1016/S1537-1891(02)00213-6 .
  3. Book: British National Formulary. 59th. British Medical Journal Publishing Group, Pharmaceutical Press. 2010. British National Formulary.
  4. News: Shire Announces Ethmozine will be Available until December 31, 2007. Heart Rhythm Society. January 12, 2012. https://web.archive.org/web/20111210094917/http://www.hrsonline.org/Policy/DevicesDrugsFDA/Drugs/Ethmozine_discontinued.cfm. December 10, 2011. dead.
  5. Cardiac Arrhythmia Suppression Trial II Investigators . Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction . The New England Journal of Medicine . 327 . 4 . 227–33 . July 1992 . 1377359 . 10.1056/NEJM199207233270403 . free .
  6. Gritsenko AN, Ermakova ZI, Zhuravlev SV . Synthesis of ethmozine, a new preparation with antiarrhythmic action . 1972 . Pharmaceutical Chemistry Journal . 6 . 9 . 575–576 . 10.1007/BF00776809 .
  7. Web site: Moracizine . Pharmaceutical Substances . Georg Thieme Verlag KG . 2024-07-02 .

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