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Identification
NameMoricizine
Accession NumberDB00680  (APRD01124)
TypeSmall Molecule
GroupsApproved, Withdrawn
Description

An antiarrhythmia agent used primarily for ventricular rhythm disturbances. [PubChem]

Structure
Thumb
Synonyms
[10-(3-Morpholin-4-yl-propionyl)-10H-phenothiazin-2-yl]-carbamic acid ethyl ester
EN-313
Ethmozin
Ethyl 10-(3-morpholinopropionyl)phenothiazine-2-carbamate
Ethyl 10-(beta-N-morpholinylpropionyl)phenothiazine-2-carbamate
Etmozin
Moracizin
Moracizina
Moracizine
Moracizinum
Moricizine
External Identifiers
  • EN-313
  • G 214
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EthmozineNot Available
EtmozinsOlainfarm
Brand mixturesNot Available
Salts
Name/CASStructureProperties
moricizine hydrochloride
ThumbNot applicableDBSALT000994
Categories
UNII2GT1D0TMX1
CAS number31883-05-3
WeightAverage: 427.517
Monoisotopic: 427.156576993
Chemical FormulaC22H25N3O4S
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Diarylthioether
  • Beta amino acid or derivatives
  • Phenylcarbamate
  • Benzenoid
  • Oxazinane
  • Morpholine
  • Para-thiazine
  • Tertiary carboxylic acid amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Thioether
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed to treat irregular heartbeats (arrhythmias) and maintain a normal heart rate.
PharmacodynamicsMoricizine 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 actionMoricizine works by inhibiting the rapid inward sodium current across myocardial cell membranes.
Related Articles
AbsorptionWell 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 bindingApproximately 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 eliminationLess 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 life2 hours (range 1.5-3.5 hours).
ClearanceNot Available
ToxicitySymptoms of overdose include vomiting, unconsciousness, and severe low blood pressure.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Shire development inc
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point156-157 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US3740395A
General ReferencesNot Available
External Links
ATC CodesC01BG01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is respon...
Gene Name:
SCN5A
Uniprot ID:
Q14524
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 ]
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Drug created on June 13, 2005 07:24 / Updated on January 13, 2014 15:20