MORICIZINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H25N3O4S.ClH
Molecular Weight	463.978
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCOC(=O)NC1=CC2=C(SC3=C(C=CC=C3)N2C(=O)CCN4CCOCC4)C=C1

InChI

InChIKey=GAQAKFHSULJNAK-UHFFFAOYSA-N

InChI=1S/C22H25N3O4S.ClH/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);1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1377359 | https://www.drugbank.ca/drugs/DB00680 | https://www.drugs.com/cons/moricizine.html | https://www.ncbi.nlm.nih.gov/pubmed/3310584

Moricizine is an antiarrhythmic agent previously marketed as Ethmozine. It was used for prophylaxis and treatment of serious and life-threatening ventricular arrhythmias. In 2007 it was withdrawn and discontinued for commercial reasons. Moricizine can be administered intravenously but was more commonly provided as an oral formulation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
voltage-gated calcium channel activity 3 Target ID: GO:0005245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8385537	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ventricular arrhythmia 50 Sources: https://clinicaltrials.gov/ct2/show/NCT00000526	Primary		Approved 8429	ETHMOZINE Approved Use Moricizine is used to correct irregular or rapid heartbeats to a normal rhythm. It is typically prescribed at a dose range of 600 - 900 mg/day, taken as 3 doses every 8 hours. Launch Date 6.457536E11

C_max

Value	Dose	Analyte	Population
0.597 mg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.607 mg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.6 mg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	250 mg 3 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.666 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2407090	200 mg 3 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
0.993 mg × h/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.138 mg × h/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.21 mg × h/L REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	250 mg 3 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.21 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2407090	200 mg 3 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.4 h REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	300 mg 3 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.5 h REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.4 h REVIEW https://pubmed.ncbi.nlm.nih.gov/2407090	250 mg 3 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2407090	200 mg 3 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	MORICIZINE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	Disc. AE: Electrocardiogram change, Congestive heart failure... AEs leading to discontinuation/dose reduction: Electrocardiogram change (17 patients) Congestive heart failure (11 patient) Atrial fibrillation (4 patients) Nausea (34 patients) Gastrointestinal upset (3 patients) Anxiety (3 patients) Hypoesthesia (2 patients) Tremor of hands (2 patients) Dyspnea (2 patients) Urinary retention (4 patients) Laboratory test abnormality (5 patients) Drug fever (3 patients) Blurred vision (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/

AEs

AE	Significance	Dose	Population
Congestive heart failure	11 patient Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Electrocardiogram change	17 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Dyspnea	2 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Hypoesthesia	2 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Tremor of hands	2 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Anxiety	3 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Blurred vision	3 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Drug fever	3 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Gastrointestinal upset	3 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Nausea	34 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Atrial fibrillation	4 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Urinary retention	4 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/
Laboratory test abnormality	5 patients Disc. AE	900 mg 1 times / day steady, oral Recommended Dose: 900 mg, 1 times / day Route: oral Route: steady Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/	unhealthy, adult n = 1256 Health Status: unhealthy Condition: arrhythmias Age Group: adult Sex: M+F Population Size: 1256 Sources: https://pubmed.ncbi.nlm.nih.gov/2407091/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A1 110 CYP1A2 1524 CYP2B 15 CYP2C 19 CYP2D 3 CYP2E1 882 CYP3A 214		CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/	no
CYP1A1 218	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/ Page:	yes [IC50 0.43 uM]	2
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/	yes [IC50 0.98 uM]
CYP2B 40	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/	yes [IC50 22.9 uM]
CYP2C 34	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/	yes [IC50 4.7 uM]
CYP2D 4	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/	yes [IC50 80 uM]
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/23121279/	yes
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12393941/	yes
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/23121279/	yes
PXR 46	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/23121279/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6997	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6997
ChemicalBook	CB4493310	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4493310
MolPort	MolPort-001-727-947	https://www.molport.com/shop/molecule-link/MolPort-001-727-947
ZINC	ZINC000019340795	http://zinc15.docking.org/substances/ZINC000019340795
eMolecules	969296	https://www.emolecules.com/cgi-bin/more?vid=969296

PubMed

Title	Date	PubMed
Proarrhythmic potential of moricizine: strengths and limitations of a data base analysis.	1990 Feb 20	1689536
The prevalence of proarrhythmic events during moricizine therapy and their relationship to ventricular function.	1992 Oct	1529903
Exercise induced fatal sinusoidal ventricular tachycardia secondary to moricizine.	1992 Oct	1383951
Effects of magnesium and ethmozin on ventricular tachycardia induced by ouabain and ventricular pacing in conscious dogs with complete atrioventricular block.	1993	8178656
Action of MgSO4 differs from moricizine and verapamil on ouabain-induced ventricular tachycardia in normomagnesemic conscious dogs.	1994 Feb	7511755
[Mechanisms of action of hypersodium medium on contractile activity of isolated rat heart].	2001	11296555
Efficacy and safety of moricizine in the maintenance of sinus rhythm in patients with recurrent atrial fibrillation.	2001 Jan 15	11152834
Moricizine, an antiarrhythmic agent, as a potent inhibitor of hepatic microsomal CYP1A.	2002 Dec	12393941
Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block.	2002 Mar	12402511
Moricizine induced increase in pacing threshold.	2003 Jan	12685150
[Moricizine in treatment of one case with tachycardia-induced cardiomyopathy].	2003 Oct	14731369
Non-linear heart rate variability and risk stratification in cardiovascular disease.	2005 Jul 1	16943869
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Bayes' Theorem to estimate population prevalence from Alcohol Use Disorders Identification Test (AUDIT) scores.	2009 Jul	19438421

Patents

Sample Use Guides

In Vivo Use Guide

Patients with greater than or equal to 30 ventricular premature complexes (VPCs) per hour were given moricizine HCL (816 +/- 103 mg daily) as a three times oral daily dose. Moricizine suppressed 81% of VPCs alone and 87% of VPCs in combination with 120 mg of propranolol.

Route of Administration: Oral

In Vitro Use Guide

Single ventricular myocytes from guinea-pig hearts were prepared by enzymatic dissociation. Isolated single cells were transferred to a recording chamber of an inverted phase-contrast microscope which was maintained at 34 - 35 deg-C. Membrane currents were recorded by using whole-cell patch-clamp technique using an amplifier. Application of 1O micro-M moricizine was started at 7 minutes and continued up to 13 minutes after the formation of whole cell configuration. In the absence of drug, the current decayed with time and the average value of relative currents at 20 min was 0.48 ± 0.11. In the presence of 10 micro-M moricizine, the tail currents decreased progressively with time and the minimum value of 0.29 was reached at 13 min after rupture of the membrane (or 6 min after the application of moricizine).

Name

Type

Language

MORICIZINE HYDROCHLORIDE

Common Name

English

MORICIZINE HYDROCHLORIDE [VANDF]

Common Name

English

MORICIZINE HYDROCHLORIDE [USP IMPURITY]

Common Name

English

MORICIZINE HYDROCHLORIDE [USP-RS]

Common Name

English

ETHMOZINE

Brand Name

English

MORICIZINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

MORACIZINE HYDROCHLORIDE

Common Name

English

MORICIZINE HCL

Common Name

English

MORICIZINE HYDROCHLORIDE [MI]

Common Name

English

MORACIZINE HYDROCHLORIDE [MART.]

Common Name

English

Moracizine hydrochloride [WHO-DD]

Common Name

English

Ethyl 10-(3-morpholinopropionyl)phenothiazine-2-carbamate, hydrochloride

Common Name

English

CARBAMIC ACID, (10-(3-(4-MORPHOLINYL)-L-OXOPROPYL)-10H-PHENOTHIAZIN-2YL)-, ETHYL ESTER, HYDROCHLORIDE

Common Name

English

EN-313

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C47793