Moricizine

Identification

Name
Moricizine
Accession Number
DB00680
Description

An antiarrhythmia agent used primarily for ventricular rhythm disturbances.

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Thumb
Weight
Average: 427.517
Monoisotopic: 427.156576993
Chemical Formula
C22H25N3O4S
Synonyms
  • [10-(3-Morpholin-4-yl-propionyl)-10H-phenothiazin-2-yl]-carbamic acid ethyl ester
  • Ethmozin
  • ethyl 10-(3-morpholinopropionyl)phenothiazine-2-carbamate
  • ethyl 10-(β-N-morpholinylpropionyl)phenothiazine-2-carbamate
  • Etmozin
  • Moracizin
  • Moracizina
  • Moracizine
  • Moracizinum
  • Moricizine
External IDs
  • EN-313
  • G 214

Pharmacology

Indication

Used to treat irregular heartbeats (arrhythmias) and maintain a normal heart rate.

Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Moricizine is used to treat irregular heartbeats (arrhythmias) and to maintain a normal heart rate. It acts on the heart muscle to improve the heart's rhythm. Moricizine has potent local anesthetic activity and membrane stabilizing effect. Decreases excitability, conduction velocity, and automaticity as a result of slowed atrioventricular (AV) nodal and His-Purkinje conduction. Decreases the action potential duration (APD) in Purkinje fibers; also decreases the effective refractory period (ERP) but to a lesser extent than the APD, so the ERP/APD ratio is increased. Decreases the maxiumum rate of Phase 0 depolarization (V max ), but does not affect action potential amplitude or maximum diastolic potential. Does not affect atrial, AV nodal, or left ventricular refractory periods and has minimal effect on ventricular repolarization (evidenced by the overall decrease in JT interval). Has no effect on sinoatrial (SA) nodal or intra-atrial conduction and only minimal effect on sinus cycle length and sinus node recovery time. In the Vaughan Williams classification of antiarrhythmics, moricizine is considered to be a class I agent. It has properties of class IA, IB, and IC agents but does not clearly belong to any of the three subclasses. It has less effect on the slope of phase 0 and a greater effect on action potential duration and effective refractory period than class IC agents.

Mechanism of action

Moricizine works by inhibiting the rapid inward sodium current across myocardial cell membranes.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Humans
Absorption

Well absorbed, absorption is complete within 2 to 3 hours. Significant first-pass metabolism results in an absolute bioavailability of approximately 38%. Administration within 30 minutes after a meal slows the rate, but does not affect the extent of absorption, although peak plasma concentrations are reduced.

Volume of distribution
  • 300 L
Protein binding

Approximately 95%.

Metabolism

Hepatic and extensive, to at least 26 metabolites, none accounting for as much as 1% of the administered dose. Two metabolites may be pharmacologically active but are present in extremely small quantities. Moricizine induces its own metabolism (it induces hepatic cytochrome P-450 activity).

Route of elimination

Less than 1% of orally administered Ethmozine® is excreted unchanged in the urine. Approximately 56% of the administered dose is excreted in the feces and 39% is excreted in the urine.

Half-life

2 hours (range 1.5-3.5 hours).

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Symptoms of overdose include vomiting, unconsciousness, and severe low blood pressure.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololMoricizine may increase the arrhythmogenic activities of Acebutolol.
AcetazolamideThe risk or severity of adverse effects can be increased when Moricizine is combined with Acetazolamide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Moricizine.
AcetophenazineThe risk or severity of adverse effects can be increased when Moricizine is combined with Acetophenazine.
AcetyldigitoxinAcetyldigitoxin may increase the arrhythmogenic activities of Moricizine.
AclidiniumMoricizine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AcrivastineThe risk or severity of QTc prolongation can be increased when Moricizine is combined with Acrivastine.
AdenosineMoricizine may increase the arrhythmogenic activities of Adenosine.
AgomelatineThe risk or severity of adverse effects can be increased when Moricizine is combined with Agomelatine.
AjmalineMoricizine may increase the arrhythmogenic activities of Ajmaline.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Product Ingredients
IngredientUNIICASInChI Key
Moricizine hydrochloride71OK3Z1ESP29560-58-5GAQAKFHSULJNAK-UHFFFAOYSA-N
Product Images
International/Other Brands
Etmozins (Olainfarm)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EthmozineTablet200 mg/1OralShire1990-06-192008-08-07US flag
EthmozineTablet300 mg/1OralShire1990-06-192008-08-07US flag
EthmozineTablet250 mg/1OralShire1990-06-192008-08-07US flag54092 04720180907 15195 di0ahn
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
C01BG01 — Moracizine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Diarylthioethers / Beta amino acids and derivatives / 1,4-thiazines / Morpholines / Benzenoids / Tertiary carboxylic acid amides / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds / Azacyclic compounds
show 6 more
Substituents
Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Beta amino acid or derivatives / Carbonyl group / Carboxamide group / Carboximidic acid derivative
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, carbamate ester, morpholines (CHEBI:6997)

Chemical Identifiers

UNII
2GT1D0TMX1
CAS number
31883-05-3
InChI Key
FUBVWMNBEHXPSU-UHFFFAOYSA-N
InChI
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)
IUPAC Name
ethyl N-{10-[3-(morpholin-4-yl)propanoyl]-10H-phenothiazin-2-yl}carbamate
SMILES
CCOC(=O)NC1=CC2=C(SC3=CC=CC=C3N2C(=O)CCN2CCOCC2)C=C1

References

Synthesis Reference
US3740395A
General References
Not Available
Human Metabolome Database
HMDB0014818
KEGG Drug
D05077
KEGG Compound
C07743
PubChem Compound
34633
PubChem Substance
46509072
ChemSpider
31872
RxNav
40169
ChEBI
6997
ChEMBL
CHEMBL1075
ZINC
ZINC000019340795
Therapeutic Targets Database
DAP000510
PharmGKB
PA164747738
Drugs.com
Drugs.com Drug Page
Wikipedia
Moricizine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedPreventionArrhythmia of ventricular origin / Cardiovascular Heart Disease / Coronary Heart Disease (CHD) / Death, Sudden,Cardiac / Heart Arrest / Heart Diseases / Myocardial Infarction / Myocardial Ischemia1
3CompletedTreatmentArrhythmia / Atrial Fibrillation (AF) / Cardiovascular Heart Disease / Heart Diseases1
2CompletedTreatmentArrhythmia / Arrhythmia of ventricular origin / Cardiovascular Heart Disease / Heart Diseases1

Pharmacoeconomics

Manufacturers
  • Shire development inc
Packagers
  • Bristol-Myers Squibb Co.
Dosage Forms
FormRouteStrength
TabletOral200 mg/1
TabletOral250 mg/1
TabletOral300 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156-157 °CPhysProp
water solubility0.457 mg/LNot Available
logP2.98SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0339 mg/mLALOGPS
logP3.04ALOGPS
logP3.07ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)12.9ChemAxon
pKa (Strongest Basic)6.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.11 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity118.88 m3·mol-1ChemAxon
Polarizability45.27 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9885
Blood Brain Barrier+0.9535
Caco-2 permeable-0.5796
P-glycoprotein substrateSubstrate0.6871
P-glycoprotein inhibitor IInhibitor0.9072
P-glycoprotein inhibitor IINon-inhibitor0.5751
Renal organic cation transporterNon-inhibitor0.8329
CYP450 2C9 substrateNon-substrate0.7472
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5274
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.6367
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7638
Ames testNon AMES toxic0.6915
CarcinogenicityNon-carcinogens0.9153
BiodegradationNot ready biodegradable0.8412
Rat acute toxicity2.4731 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9229
hERG inhibition (predictor II)Inhibitor0.732
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. 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. Vascul Pharmacol. 2002 Mar;38(3):131-41. [PubMed:12402511]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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