Moracizine

Moracizine
Clinical data
Trade namesEthmozine
Other namesMoricizine (USAN US)
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa601214
Pregnancy
category
ATC code
Pharmacokinetic data
Bioavailability34–38%
Protein binding95%
Elimination half-life3–4 hours (healthy volunteers), 6–13 hours (cardiac disease)
Identifiers
  • ethyl [10-(3-morpholin-4-ylpropanoyl)-10H-phenothiazin-2-yl]carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.046.216 Edit this at Wikidata
Chemical and physical data
FormulaC22H25N3O4S
Molar mass427.52 g·mol−1
3D model (JSmol)
  • O=C(OCC)Nc2cc1N(c3c(Sc1cc2)cccc3)C(=O)CCN4CCOCC4
  • InChI=1S/C22H25N3O4S/c1-2-29-22(27)23-16-7-8-20-18(15-16)25(17-5-3-4-6-19(17)30-20)21(26)9-10-24-11-13-28-14-12-24/h3-8,15H,2,9-14H2,1H3,(H,23,27) checkY
  • Key:FUBVWMNBEHXPSU-UHFFFAOYSA-N checkY

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It was used for the prophylaxis and treatment of serious and life-threatening ventricular arrhythmias,[3] but was withdrawn in 2007 for commercial reasons.[4]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.[citation needed] Compared with disopyramide and quinidine, moracizine was equally or more effective in suppressing premature ventricular contractions, couplets, and nonsustained ventricular tachycardia.[citation needed]

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

References

  1. ^ "The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances" (PDF). World Health Organization. 2009. p. 103.
  2. ^ Ahmmed GU, Hisatome I, Kurata Y, Makita N, Tanaka Y, Tanaka H, et al. (March 2002). "Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block". Vascular Pharmacology. 38 (3): 131–41. doi:10.1016/S1537-1891(02)00213-6. PMID 12402511.
  3. ^ British National Formulary (59th ed.). British Medical Journal Publishing Group, Pharmaceutical Press. 2010.
  4. ^ "Shire Announces Ethmozine will be Available until December 31, 2007". Heart Rhythm Society. Archived from the original on December 10, 2011. Retrieved January 12, 2012.
  5. ^ Cardiac Arrhythmia Suppression Trial II Investigators (July 1992). "Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction". The New England Journal of Medicine. 327 (4): 227–33. doi:10.1056/NEJM199207233270403. PMID 1377359.
  6. ^ Gritsenko AN, Ermakova ZI, Zhuravlev SV (1972). "Synthesis of ethmozine, a new preparation with antiarrhythmic action". Pharmaceutical Chemistry Journal. 6 (9): 575–576. doi:10.1007/BF00776809.
  7. ^ "Moracizine". Pharmaceutical Substances. Georg Thieme Verlag KG. Retrieved 2024-07-02.
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