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
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
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: picrotoxin/barbiturate site of the GABAA-receptor-chloride channel complex Sources: https://www.ncbi.nlm.nih.gov/pubmed/2544811 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Heminevrin Approved UseClomethiazole 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. |
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Primary | Heminevrin Approved UseClomethiazole 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. |
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Primary | Heminevrin Approved UseClomethiazole 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. |
PubMed
Title | Date | PubMed |
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Focal dystonic reaction to phenytoin. | 1984 Oct |
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The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole. | 1992 Apr |
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Chlormethiazole: effectiveness against toxic effects of cocaine in mice. | 2000 Oct |
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Current status and perspectives of neuroprotection in ischemic stroke treatment. | 2001 |
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Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole. A pilot study. | 2001 Aug |
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Neuroprotective efficacy of AR-A008055, a clomethiazole analogue, in a global model of acute ischaemic stroke and its effect on ischaemia-induced glutamate and GABA efflux in vitro. | 2001 Aug |
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[Clomethiazole as an adjuvant in the treatment of confusional psychosis]. | 2001 Jun |
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The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results. | 2001 Oct 9 |
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Neuroprotective agents in acute ischemic stroke. | 2002 Feb |
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Clomethiazole: an unsuccessful bachelor, but perhaps a prosperous married man? | 2002 Jan |
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[Diagnosis and treatment of delirium]. | 2002 Mar 13 |
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The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1beta-induced neurodegeneration. | 2003 |
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Population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients. | 2003 Aug |
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The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. | 2003 Jul |
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Pharmacokinetics and sedative effects in healthy subjects and subjects with impaired liver function after continuous infusion of clomethiazole. | 2003 Jun |
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Comparison of the neuroprotective effect of clomethiazole, AR-R15896AR and NXY-059 in a primate model of stroke using histological and behavioural measures. | 2003 May 16 |
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Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial. | 2003 Oct |
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Changes in fatalities due to overdose of anxiolytic and sedative drugs in the UK (1983-1999). | 2004 |
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Chlormethiazole potentiates the discriminative stimulus effects of methamphetamine in rats. | 2004 Jun 28 |
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Polysomnography during withdrawal with clomethiazole or placebo in alcohol dependent patients--a double-blind and randomized study. | 2004 Sep |
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Alcohol, vitamin A, and cancer. | 2005 Apr |
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The effects of clomethiazole on polysomnographically recorded sleep in healthy subjects. | 2005 Aug |
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Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus. | 2005 Aug 22 |
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Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia. | 2005 Sep |
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Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats. | 2006 Apr |
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Ubiquitin-dependent degradation of p53 protein despite phosphorylation at its N terminus by acetaminophen. | 2006 Apr |
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Reduced baroreflex sensitivity in acute alcohol withdrawal syndrome and in abstained alcoholics. | 2006 Oct 15 |
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Clinical studies with oral lipid based formulations of poorly soluble compounds. | 2007 Aug |
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Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration. | 2007 Jan 19 |
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Treatment with clomethiazole is associated with lower rates of premature discharge during alcohol withdrawal. | 2008 Jul |
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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 |
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[Anticonvulsants in the treatment of alcoholism]. | 2009 Apr |
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[Use of combined treatment with melatonin and clomethiazole in circadian rhythm sleep disorder in the elderly with dementia]. | 2009 Jul-Aug |
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Gamma hydroxybutyric acid (GHB) for the treatment of alcohol dependence: a review. | 2009 Jun |
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[Pharmacotherapy of substance dependence and withdrawal syndromes]. | 2009 Jun |
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Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT. | 2009 Sep |
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Medications acting on the GABA system in the treatment of alcoholic patients. | 2010 |
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Impaired cerebral autoregulation during acute alcohol withdrawal. | 2010 Aug 1 |
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Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence. | 2010 Dec 14 |
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Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice. | 2011 Aug 15 |
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Ethanol induction of CYP2A5: role of CYP2E1-ROS-Nrf2 pathway. | 2012 Aug |
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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 |
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Inhibition of cytochrome P4502E1 by chlormethiazole attenuated acute ethanol-induced fatty liver. | 2014 Oct 5 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.medicines.org.uk/emc/medicine/33156
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11082484
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.
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19035073
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6001-74-7
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m3645
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85223EMG44
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DBSALT002018
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ACTIVE MOIETY
SUBSTANCE RECORD