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
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)
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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Anticonvulsant-induced status epilepticus in Lennox-Gastaut syndrome. | 1981 Feb |
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Focal dystonic reaction to phenytoin. | 1984 Oct |
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A single-dose study of the pharmacodynamic effects of chlormethiazole, temazepam and placebo in elderly parkinsonian patients. | 1991 Nov |
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Inhibition of CYP2E1 activity does not abolish pulsatile urine alcohol concentrations during chronic alcohol infusions. | 1995 Jun 15 |
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Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole. A pilot study. | 2001 Aug |
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A study of the mechanisms involved in the neurotoxic action of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') on dopamine neurones in mouse brain. | 2001 Dec |
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Neuroprotective agents in acute ischemic stroke. | 2002 Feb |
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Gateways to clinical trials. | 2002 May |
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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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Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial. | 2003 Oct |
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Clomethiazole alters immune function within an isolated cardiopulmonary bypass circuit. | 2004 Apr |
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Generic three-column parallel LC-MS/MS system for high-throughput in vitro screens. | 2004 Nov 26 |
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Alcohol, vitamin A, and cancer. | 2005 Apr |
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Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia. | 2005 Sep |
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Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal. | 2005 Sep |
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Chorea induced by low-dose trazodone. | 2006 |
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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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Reduced baroreflex sensitivity in acute alcohol withdrawal syndrome and in abstained alcoholics. | 2006 Oct 15 |
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Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome. | 2006 Sep |
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Clinical studies with oral lipid based formulations of poorly soluble compounds. | 2007 Aug |
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[Carbamazepine intoxication. Complication of alcohol detoxification with combined carbamazepine and tiapride]. | 2007 Jan |
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Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration. | 2007 Jan 19 |
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Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. | 2007 Jul |
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AMPA receptor activation reduces epileptiform activity in the rat neocortex. | 2007 Jul 16 |
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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 Mar |
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Angiogenesis as a predictive marker of neurological outcome following hypoxia-ischemia. | 2007 Sep 26 |
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Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury. | 2008 |
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The effectiveness of anticonvulsants in psychiatric disorders. | 2008 |
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Treatment with clomethiazole is associated with lower rates of premature discharge during alcohol withdrawal. | 2008 Jul |
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A comprehensive functional analysis of tissue specificity of human gene expression. | 2008 Nov 12 |
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Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines. | 2009 |
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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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Characterization of cardamonin metabolism by P450 in different species via HPLC-ESI-ion trap and UPLC-ESI-quadrupole mass spectrometry. | 2009 Oct |
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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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An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol. | 2010 Mar-Apr |
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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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100000085629
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C034739
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20802
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1867-58-9
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22NJI0W1D2
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m3645
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9892648
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DTXSID40940133
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SUB01358MIG
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217-483-0
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD