Moricizine
Identification
- Summary
Moricizine is an antiarrhythmic used to treat arrhythmias.
- Generic Name
- Moricizine
- DrugBank Accession Number
- DB00680
- Background
An antiarrhythmia agent used primarily for ventricular rhythm disturbances.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
- 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.
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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.
Target Actions Organism ASodium channel protein type 5 subunit alpha inhibitorHumans - 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
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- Toxicity
Symptoms of overdose include vomiting, unconsciousness, and severe low blood pressure.
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Moricizine is combined with 1,2-Benzodiazepine. Acebutolol Moricizine may increase the arrhythmogenic activities of Acebutolol. Acetazolamide The risk or severity of CNS depression can be increased when Moricizine is combined with Acetazolamide. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Moricizine. Acetophenazine The risk or severity of CNS depression can be increased when Moricizine is combined with Acetophenazine. - Food Interactions
- Not Available
Products
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- Product Ingredients
Ingredient UNII CAS InChI Key Moricizine hydrochloride 71OK3Z1ESP 29560-58-5 GAQAKFHSULJNAK-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Etmozins (Olainfarm)
- Brand Name Prescription Products
Categories
- ATC Codes
- C01BG01 — Moracizine
- Drug Categories
- Antiarrhythmic agents
- Antiarrhythmics, Class I
- Antiarrhythmics, Class Ic
- Antipsychotic Agents
- Cardiac Therapy
- Cardiovascular Agents
- Central Nervous System Depressants
- Heterocyclic Compounds, Fused-Ring
- Membrane Transport Modulators
- Morpholines
- Neurotoxic agents
- Oxazines
- Phenothiazines
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Sodium Channel Blockers
- Sulfur Compounds
- Voltage-Gated Sodium Channel Blockers
- 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)
- Affected organisms
- Humans and other mammals
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
- External Links
- Human Metabolome Database
- HMDB0014818
- KEGG Drug
- D05077
- KEGG Compound
- C07743
- PubChem Compound
- 34633
- PubChem Substance
- 46509072
- ChemSpider
- 31872
- 40169
- ChEBI
- 6997
- ChEMBL
- CHEMBL1075
- ZINC
- ZINC000019340795
- Therapeutic Targets Database
- DAP000510
- PharmGKB
- PA164747738
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Moracizine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Prevention Cardiac Arrest / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Myocardial Infarction / Myocardial Ischemia / Sudden Cardiac Death / Ventricular Arrhythmia 1 3 Completed Treatment Arrhythmia / Atrial Fibrillation / Cardiovascular Disease (CVD) 1 2 Completed Treatment Arrhythmia / Cardiovascular Disease (CVD) / Ventricular Arrhythmia 1
Pharmacoeconomics
- Manufacturers
- Shire development inc
- Packagers
- Bristol-Myers Squibb Co.
- Dosage Forms
Form Route Strength Tablet Oral 200 mg/1 Tablet Oral 250 mg/1 Tablet Oral 300 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 156-157 °C PhysProp water solubility 0.457 mg/L Not Available logP 2.98 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.0339 mg/mL ALOGPS logP 3.04 ALOGPS logP 3.07 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 12.9 Chemaxon pKa (Strongest Basic) 6.73 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 71.11 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 118.88 m3·mol-1 Chemaxon Polarizability 45.27 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9885 Blood Brain Barrier + 0.9535 Caco-2 permeable - 0.5796 P-glycoprotein substrate Substrate 0.6871 P-glycoprotein inhibitor I Inhibitor 0.9072 P-glycoprotein inhibitor II Non-inhibitor 0.5751 Renal organic cation transporter Non-inhibitor 0.8329 CYP450 2C9 substrate Non-substrate 0.7472 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.5274 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.6367 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7638 Ames test Non AMES toxic 0.6915 Carcinogenicity Non-carcinogens 0.9153 Biodegradation Not ready biodegradable 0.8412 Rat acute toxicity 2.4731 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9229 hERG inhibition (predictor II) Inhibitor 0.732
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0inc-3369000000-87e2c170cd925eacc845 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0100900000-63270ad59ec0af5d64a1 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0059-1019800000-e2a5da932dba17b1d762 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0ugi-0208900000-6a9959d71f68922aced1 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00os-1098700000-36059eb9532e2a1a14f7 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00no-2459300000-3692f9e7d18fbc98ee49 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-015a-0093000000-1ae2ac95fa67ece38b72 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 213.4669963 predictedDarkChem Lite v0.1.0 [M-H]- 197.49797 predictedDeepCCS 1.0 (2019) [M+H]+ 213.8485963 predictedDarkChem Lite v0.1.0 [M+H]+ 199.85597 predictedDeepCCS 1.0 (2019) [M+Na]+ 213.7307963 predictedDarkChem Lite v0.1.0 [M+Na]+ 206.81265 predictedDeepCCS 1.0 (2019)
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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:59