CHLORMEZANONE, (+)-

US Previously Marketed

First approved in 1958

Details

Stereochemistry	UNKNOWN
Molecular Formula	C11H12ClNO3S
Molecular Weight	273.736
Optical Activity	( + )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(C2=CC=C(Cl)C=C2)S(=O)(=O)CCC1=O

InChI

InChIKey=WEQAYVWKMWHEJO-UHFFFAOYSA-N

InChI=1S/C11H12ClNO3S/c1-13-10(14)6-7-17(15,16)11(13)8-2-4-9(12)5-3-8/h2-5,11H,6-7H2,1H3

HIDE SMILES / InChI

Molecular Formula	C11H12ClNO3S
Molecular Weight	273.736
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: www.ncbi.nlm.nih.gov/mesh/68002720
Curator's Comment: description was created based on several sources, including http://www.who.int/medicines/publications/drugalerts/drug_alert53chlormezanone_serious_cutaneous_reactions.pdf | https://www.drugbank.ca/drugs/DB01178

Chlormezanone (TRANCOPAL®) is a non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm. It binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways. Chlormezanone (TRANCOPAL®) was discontinued worldwide in 1996 by Sanofi due to confirmed serious and rare cutaneous reactions (toxic epidermal necrolysis also known as Stevens-Johnson syndrome).

CNS Activity

Originator

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Muscle spasm 40 Sources: https://www.ncbi.nlm.nih.gov/mesh/68002720	Primary		Withdrawn	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
4.62 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2399514	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORMEZANONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
164.19 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2399514	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CHLORMEZANONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
224.93 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2399514	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORMEZANONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
37.14 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2399514	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CHLORMEZANONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
40.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/2399514	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORMEZANONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
4 g single, oral Overdose Dose: 4 g Route: oral Route: single Dose: 4 g Co-administed with:: acetaminophen, p.o(18 g) Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.45	healthy, 46 n = 1 Health Status: healthy Age Group: 46 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.45	Disc. AE: Coma... AEs leading to discontinuation/dose reduction: Coma (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.45
400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45	unhealthy n = 10 Health Status: unhealthy Condition: Painful muscular spasms Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45	Disc. AE: Muscular weakness, Ataxia... AEs leading to discontinuation/dose reduction: Muscular weakness Ataxia Stumbling Tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45
800 mg single, oral Studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44	unhealthy n = 5 Health Status: unhealthy Condition: Painful muscular spasms Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44	Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44

AEs

AE	Significance	Dose	Population
Coma	grade 5 Disc. AE	4 g single, oral Overdose Dose: 4 g Route: oral Route: single Dose: 4 g Co-administed with:: acetaminophen, p.o(18 g) Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.45	healthy, 46 n = 1 Health Status: healthy Age Group: 46 Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.45
Ataxia	Disc. AE	400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45	unhealthy n = 10 Health Status: unhealthy Condition: Painful muscular spasms Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45
Muscular weakness	Disc. AE	400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45	unhealthy n = 10 Health Status: unhealthy Condition: Painful muscular spasms Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45
Stumbling	Disc. AE	400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45	unhealthy n = 10 Health Status: unhealthy Condition: Painful muscular spasms Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45
Tachycardia	Disc. AE	400 mg 3 times / day multiple, oral Recommended Dose: 400 mg, 3 times / day Route: oral Route: multiple Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45	unhealthy n = 10 Health Status: unhealthy Condition: Painful muscular spasms Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/1936060 Page: p.44, p.45

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3619	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3619
ChemicalBook	CB8355331	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8355331
MolPort	MolPort-003-666-762	https://www.molport.com/shop/molecule-link/MolPort-003-666-762
Selleck Chemicals	Chlormezanone(Trancopal)	http://www.selleckchem.com/products/Chlormezanone(Trancopal).html
eMolecules	1934274	https://www.emolecules.com/cgi-bin/more?vid=1934274

PubMed

Title	Date	PubMed
Drug-related gustatory disorders.	1978 Jan-Feb	623418
[Drug-induced hepatitis with cholestasis following therapy with chlormezanone].	1985 Dec	4090569
[Pharmacokinetics of chlormezanone in healthy volunteers].	1990 Jul-Aug	2399514
[New findings on the synthesis of the centrally acting muscle relaxant chlormezanone and its resolution of a gram scale using a Chiralcel OD column].	2003 Feb	12641322
Stimulatory effects of chlorzoxazone, a centrally acting muscle relaxant, on large conductance calcium-activated potassium channels in pituitary GH3 cells.	2003 Jan 3	12480161
Investigations of interactions of chlormezanone racemate and its enantiomers on human keratinocytes and human leucoytes in vitro.	2005 May-Jun	15897685
Fixed drug eruption resulting from fluconazole use: a case report.	2009 Jul 6	19830193
Toxic epidermal necrolysis and Stevens-Johnson syndrome.	2010 Dec 16	21162721
Flupirtine in pain management: pharmacological properties and clinical use.	2010 Oct	20839897

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Oral

In Vitro Use Guide

The investigation was performed in order to investigate whether the racemic chlormezanone and both enantiomers differ in their potential cytotoxicty for human HaCaT keratinocytes. In the dosage range of 0.001 to 0.1 mg/ml chlormezanone, no antiproliferative effects were measured with the racemate and both enantiomers. At 1.0 mg/ml, a decrease of proliferative activity was seen after 48 h incubation time of about 50% for the enantiomers and of about 80% for the racemate (PicoGreen assay) and 50% (enantiomers) or 21% (racemate) in the ATP assay, respectively. Oxygen radicals production by human interleukin-3-stimulated leukocytes was significantly inhibited at concentrations < or =0.01 mg/ml by the racemate and the (+)-enantiomer, whereas the (-)-enantiomer was less effective.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:24:43 UTC 2023` Edited by `admin` on `Sat Dec 16 10:24:43 UTC 2023`
Record UNII	4BU37OM8KL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CHLORMEZANONE, (+)-

Common Name

English

4H-1,3-THIAZIN-4-ONE, 2-(4-CHLOROPHENYL)TETRAHYDRO-3-METHYL-, 1,1-DIOXIDE, (+)-

Systematic Name

English

(+)-FENAROL

Common Name

English

(+)-CHLORMEZANONE

Common Name

English

Code System Code Type Description

FDA UNII

4BU37OM8KL

Created by admin on Sat Dec 16 10:24:43 UTC 2023 , Edited by admin on Sat Dec 16 10:24:43 UTC 2023

PRIMARY

CAS

102818-66-6

Created by admin on Sat Dec 16 10:24:43 UTC 2023 , Edited by admin on Sat Dec 16 10:24:43 UTC 2023

PRIMARY

Related Record Type Details


					GP568V9G19

CHLORMEZANONE

RACEMATE -> ENANTIOMER

Amount:

Details

SMILES

InChI

DescriptionSources: www.ncbi.nlm.nih.gov/mesh/68002720Curator's Comment: description was created based on several sources, including http://www.who.int/medicines/publications/drugalerts/drug_alert53chlormezanone_serious_cutaneous_reactions.pdf | https://www.drugbank.ca/drugs/DB01178

CNS Activity

Originator

Approval Year

Conditions

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: www.ncbi.nlm.nih.gov/mesh/68002720
Curator's Comment: description was created based on several sources, including http://www.who.int/medicines/publications/drugalerts/drug_alert53chlormezanone_serious_cutaneous_reactions.pdf | https://www.drugbank.ca/drugs/DB01178

C_max

T_1/2