U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula 2C6H8ClNS.C2H6O6S2
Molecular Weight 513.5
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLOMETHIAZOLE EDISYLATE

SMILES

CC1=C(CCCl)SC=N1.CC2=C(CCCl)SC=N2.OS(=O)(=O)CCS(O)(=O)=O

InChI

InChIKey=WFVBVWRCFZCWJU-UHFFFAOYSA-N
InChI=1S/2C6H8ClNS.C2H6O6S2/c2*1-5-6(2-3-7)9-4-8-5;3-9(4,5)1-2-10(6,7)8/h2*4H,2-3H2,1H3;1-2H2,(H,3,4,5)(H,6,7,8)

HIDE SMILES / InChI

Molecular Formula C2H6O6S2
Molecular Weight 190.195
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C6H8ClNS
Molecular Weight 161.652
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Chlormethiazole has sedative, hypnotic, anticonvulsant and neuroprotective properties. This drug is approved in different counties under the different brand name (e.g., Heminevrin) and is used for the management of restlessness and agitation in the elderly, short-term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms. Clomethiazole interacts with the picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex. Clomethiazole is pharmacologically distinct from both the benzodiazepines and the barbiturates. Given alone its effects on respiration are slight and the therapeutic index high.

Originator

Curator's Comment: # Hoffmann-La Roche

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Heminevrin

Approved Use

Clomethiazole is a short acting hypnotic and sedative with anticonvulsant effect. It is used for the: management of restlessness and agitation in the elderly, short term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms where close hospital supervision is also provided.
Primary
Heminevrin

Approved Use

Clomethiazole is a short acting hypnotic and sedative with anticonvulsant effect. It is used for the: management of restlessness and agitation in the elderly, short term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms where close hospital supervision is also provided.
Primary
Heminevrin

Approved Use

Clomethiazole is a short acting hypnotic and sedative with anticonvulsant effect. It is used for the: management of restlessness and agitation in the elderly, short term treatment of severe insomnia in the elderly and treatment of alcohol withdrawal symptoms where close hospital supervision is also provided.
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.55 μg/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.4 μg/mL
600 mg single, rectal
dose: 600 mg
route of administration: Rectal
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
40 μM
265 μmol/kg single, intravenous
dose: 265 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
33 μM
265 μmol/kg single, intravenous
dose: 265 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
39 μM
265 μmol/kg single, intravenous
dose: 265 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.95 μg/mL
192 mg single, oral
dose: 192 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.27 μg/mL
192 mg single, oral
dose: 192 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
110.8 μg × min/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
73.2 μg × min/mL
600 mg single, rectal
dose: 600 mg
route of administration: Rectal
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
224 mg × min/L
162 mg single, intravenous
dose: 162 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
149 mg × min/L
162 mg single, intravenous
dose: 162 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
303 mg × min/L
192 mg single, oral
dose: 192 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
17.5 mg × min/L
192 mg single, oral
dose: 192 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10 h
265 μmol/kg single, intravenous
dose: 265 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
12 h
265 μmol/kg single, intravenous
dose: 265 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
19 h
265 μmol/kg single, intravenous
dose: 265 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8.7 h
162 mg single, intravenous
dose: 162 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.6 h
162 mg single, intravenous
dose: 162 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8.9 h
192 mg single, oral
dose: 192 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
44.2%
CLOMETHIAZOLE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
35.6%
CLOMETHIAZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
390 mg single, oral
Studied dose
Dose: 390 mg
Route: oral
Route: single
Dose: 390 mg
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
390 mg single, rectal
Studied dose
Dose: 390 mg
Route: rectal
Route: single
Dose: 390 mg
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Disc. AE: Somnolence...
Other AEs: Somnolence, Rhinitis...
AEs leading to
discontinuation/dose reduction:
Somnolence (15.6%)
Other AEs:
Somnolence (53%)
Rhinitis (19%)
Fever (17%)
Headache (12%)
Hypertension (8%)
Coughing (7%)
Yawning (7%)
Sputum increased (5%)
Agitation (5%)
Somnolence (3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Headache 12%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Somnolence 15.6%
Disc. AE
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Fever 17%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Rhinitis 19%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Somnolence 3%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Agitation 5%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Sputum increased 5%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Somnolence 53%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Coughing 7%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Yawning 7%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Hypertension 8%
75 mg/kg single, intravenous
Studied dose
Dose: 75 mg/kg
Route: intravenous
Route: single
Dose: 75 mg/kg
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
PubMed

PubMed

TitleDatePubMed
Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver.
2014-10-05
CMZ reversed chronic ethanol-induced disturbance of PPAR-α possibly by suppressing oxidative stress and PGC-1α acetylation, and activating the MAPK and GSK3β pathway.
2014
Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway.
2012-08
Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice.
2011-08-15
Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence.
2010-12-14
Impaired cerebral autoregulation during acute alcohol withdrawal.
2010-08-01
Medications acting on the GABA system in the treatment of alcoholic patients.
2010
An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol.
2009-12-19
Characterization of cardamonin metabolism by P450 in different species via HPLC-ESI-ion trap and UPLC-ESI-quadrupole mass spectrometry.
2009-10
Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT.
2009-09
Gamma hydroxybutyric acid (GHB) for the treatment of alcohol dependence: a review.
2009-06
[Pharmacotherapy of substance dependence and withdrawal syndromes].
2009-06
[Anticonvulsants in the treatment of alcoholism].
2009-04
[Use of combined treatment with melatonin and clomethiazole in circadian rhythm sleep disorder in the elderly with dementia].
2009-01-19
Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines.
2009
Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: an open, single-center randomized study.
2009
A comprehensive functional analysis of tissue specificity of human gene expression.
2008-11-12
Treatment with clomethiazole is associated with lower rates of premature discharge during alcohol withdrawal.
2008-07
Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury.
2008
The effectiveness of anticonvulsants in psychiatric disorders.
2008
Angiogenesis as a predictive marker of neurological outcome following hypoxia-ischemia.
2007-09-26
Clinical studies with oral lipid based formulations of poorly soluble compounds.
2007-08
AMPA receptor activation reduces epileptiform activity in the rat neocortex.
2007-07-16
Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study.
2007-07
Measurement properties of the National Institutes of Health Stroke Scale for people with right- and left-hemisphere lesions: further analysis of the clomethiazole for acute stroke study-ischemic (class-I) trial.
2007-03
Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration.
2007-01-19
[Carbamazepine intoxication. Complication of alcohol detoxification with combined carbamazepine and tiapride].
2007-01
Reduced baroreflex sensitivity in acute alcohol withdrawal syndrome and in abstained alcoholics.
2006-10-15
Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome.
2006-09
Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats.
2006-04
Ubiquitin-dependent degradation of p53 protein despite phosphorylation at its N terminus by acetaminophen.
2006-04
Chorea induced by low-dose trazodone.
2006
Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia.
2005-09
Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal.
2005-09
Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus.
2005-08-22
The effects of clomethiazole on polysomnographically recorded sleep in healthy subjects.
2005-08
Clomethiazole: mechanisms underlying lasting neuroprotection following hypoxia-ischemia.
2005-06
Rapid and long-lasting tolerance to clomethiazole-induced hypothermia in the rat.
2005-04-11
Alcohol, vitamin A, and cancer.
2005-04
Treatment of alcohol withdrawal syndrome with combined carbamazepine and tiapride in a patient with probable sleep apnoe syndrome.
2005-03
Generic three-column parallel LC-MS/MS system for high-throughput in vitro screens.
2004-11-26
Factor analysis of the National Institutes of Health Stroke Scale in patients with large strokes.
2004-11
Polysomnography during withdrawal with clomethiazole or placebo in alcohol dependent patients--a double-blind and randomized study.
2004-09
Inhibition of CYP2E1 activity does not abolish pulsatile urine alcohol concentrations during chronic alcohol infusions.
1995-06-15
Sudden death after intravenous application of lorazepam in a patient treated with clozapine.
1994-05
Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.
1993-03
A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients.
1991-11
Focal dystonic reaction to phenytoin.
1984-10
Anticonvulsant-induced status epilepticus in Lennox-Gastaut syndrome.
1981-02
Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia.
1979-01
Patents

Sample Use Guides

Management of restlessness and agitation in the elderly: one capsule three times daily. Severe insomnia in the elderly: 1 - 2 capsules before going to bed. The lower dose should be tried first. As with all psychotropic drugs, treatment should be kept to a minimum, reviewed regularly and discontinued as soon as possible. Alcohol withdrawal states: Clomethiazole is not a specific 'cure' for alcoholism. Alcohol withdrawal should be treated in hospital or, in exceptional circumstances, on an outpatient basis by specialist units when the daily dosage of clomethiazole must be monitored closely by community health staff. The dosage should be adjusted to patient response. The patient should be sedated but rousable. A suggested regimen is: Initial dose: Day 1, first 24 hours: Day 2: Day 3: Days 4 to 6: 2 to 4 capsules, if necessary repeated after some hours. 9 to 12 capsules, divided into 3 or 4 doses. 6 to 8 capsules, divided into 3 or 4 doses. 4 to 6 capsules, divided into 3or 4 doses. A gradual reduction in dosage until the final dose.
Route of Administration: Oral
Using in vitro grease-gap recordings, it was shown that chlormethiazole inhibited epileptiform activity in neocortical slices superfused with Mg(2+)-free medium (IC(50) approximately 200 microM). At an antiepileptic concentration (300 microM), chlormethiazole potentiated the action of exogenously applied GABA (1 mM) but did not affect responses to the glutamate receptor agonists N-methyl-D-aspartate (10 microM) or L-quisqualic acid (3 microM). The GABA(A) receptor antagonist N-methyl-bicuculline (50 microM) reduced chlormethiazole's potency to inhibit the epileptiform activity. These results indicated that chlormethiazole's anticonvulsant action was likely mediated by potentiating GABA(A)ergic inhibition rather than by antagonising glutamatergic excitation.
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:48:58 GMT 2025
Edited
by admin
on Mon Mar 31 17:48:58 GMT 2025
Record UNII
22NJI0W1D2
Record Status Validated (UNII)
Record Version
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Name Type Language
CLOMETHIAZOLE EDISYLATE
Common Name English
CLOMETHIAZOLE ETHANEDISULFONATE
MI  
Preferred Name English
SCTZ
Common Name English
CLOMETHIAZOLE EDISILATE [MART.]
Common Name English
CLOMETHIAZOLE ETHANEDISULFONATE [MI]
Common Name English
NEX-002
Code English
5-(2-CHLOROETHYL)-4-METHYLTHIAZOLE ETHANE-1,2-DISULPHONATE
Systematic Name English
Clomethiazole edisilate [WHO-DD]
Common Name English
Code System Code Type Description
SMS_ID
100000085629
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
MESH
C034739
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
RXCUI
20802
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY RxNorm
CAS
1867-58-9
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
FDA UNII
22NJI0W1D2
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
MERCK INDEX
m3645
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY Merck Index
PUBCHEM
9892648
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
EPA CompTox
DTXSID40940133
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
EVMPD
SUB01358MIG
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
ECHA (EC/EINECS)
217-483-0
Created by admin on Mon Mar 31 17:48:58 GMT 2025 , Edited by admin on Mon Mar 31 17:48:58 GMT 2025
PRIMARY
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ACTIVE MOIETY