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Details

Stereochemistry ACHIRAL
Molecular Formula C6H8ClNS.ClH
Molecular Weight 198.113
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CLOMETHIAZOLE HYDROCHLORIDE

SMILES

Cl.CC1=C(CCCl)SC=N1

InChI

InChIKey=OFXYKSLKNMTBHK-UHFFFAOYSA-N
InChI=1S/C6H8ClNS.ClH/c1-5-6(2-3-7)9-4-8-5;/h4H,2-3H2,1H3;1H

HIDE SMILES / InChI

Description

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.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Heminevrin
Primary
Heminevrin
Primary
Heminevrin

Cmax

ValueDoseCo-administeredAnalytePopulation
1.55 μg/mL
600 mg single, oral
CLOMETHIAZOLE serum
Homo sapiens
0.4 μg/mL
600 mg single, rectal
CLOMETHIAZOLE serum
Homo sapiens
40 μM
265 μmol/kg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
33 μM
265 μmol/kg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
39 μM
265 μmol/kg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
1.95 μg/mL
192 mg single, oral
CLOMETHIAZOLE plasma
Homo sapiens
0.27 μg/mL
192 mg single, oral
CLOMETHIAZOLE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
110.8 μg × min/mL
600 mg single, oral
CLOMETHIAZOLE serum
Homo sapiens
73.2 μg × min/mL
600 mg single, rectal
CLOMETHIAZOLE serum
Homo sapiens
224 mg × min/L
162 mg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
149 mg × min/L
162 mg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
303 mg × min/L
192 mg single, oral
CLOMETHIAZOLE plasma
Homo sapiens
17.5 mg × min/L
192 mg single, oral
CLOMETHIAZOLE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
10 h
265 μmol/kg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
12 h
265 μmol/kg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
19 h
265 μmol/kg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
8.7 h
162 mg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
6.6 h
162 mg single, intravenous
CLOMETHIAZOLE plasma
Homo sapiens
8.9 h
192 mg single, oral
CLOMETHIAZOLE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
44.2%
CLOMETHIAZOLE plasma
Homo sapiens
35.6%
CLOMETHIAZOLE plasma
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.