関: clomethiazole

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/03/27 21:45:50」(JST)

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Clomethiazole (also called chlormethiazole) is a sedative and hypnotic originally developed by Hoffmann-Le Roche in the 1930s.^[1] The drug is used in treating and preventing symptoms of acute alcohol withdrawal.

It is a drug which is structurally related to thiamine (vitamin B₁) but acts like a sedative, hypnotic, muscle relaxant and anticonvulsant. It is also used for the management of agitation, restlessness, short-term insomnia and Parkinson's disease in the elderly. In the U.K, it is sold under the brand Heminevrin (AstraZeneca Pharmaceuticals). Another brand name includes Nevrin (in Romania) or Distraneurin in Germany. The drug is marketed either as a free base in an oily suspension containing 192 mg in capsule form, or as clomethiazole edisylate syrup.

Pharmacology

Chlomethiazole acts as a positive allosteric modulator at the barbiturate/picrotoxin site of the GABA-A receptor. It works to enhance the action of the neurotransmitter GABA at this receptor.^{[citation needed]}GABA is the major inhibitory neurotransmitter in the brain and produces anxiolytic, anticonvulsant, sedative, and hypnotic effects. Chlomethiazole appears to also have another mechanism of action mediating some of its hypothermic and neuroprotective effects.^{[citation needed]}

Adverse effects

Long term and frequent use of chlomethiazole can cause tolerance and physical dependence. Abrupt withdrawal may result in symptoms similar to those of sudden withdrawal of alcohol or benzodiazepines.^[2]

Overdose

Chlomethiazole is particularly toxic and dangerous in overdose and can be potentially fatal.^[3]

References

^ CH patent 200248, "Verfahren zur Darstellung von 4-Methyl-5-B-chloräthylthiazol", issued 1938-09-30, assigned to Hoffmann-La Roche
^ Reilly, T. M. (1976). "Physiological dependence on, and symptoms of withdrawal from, chlormethiazole". The British Journal of Psychiatry 128: 375–378. doi:10.1192/bjp.128.4.375. PMID 1260235. edit
^ Reith, D. M.; Fountain, J.; McDowell, R.; Tilyard, M. (2003). "Comparison of the fatal toxicity index of zopiclone with benzodiazepines". Clinical Toxicology 41 (7): 975–980. doi:10.1081/CLT-120026520. PMID 14705844. edit

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English Journal

Estrogen-related receptor γ controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol.

Kim DK, Kim YH, Jang HH, Park J, Kim JR, Koh M, Jeong WI, Koo SH, Park TS, Yun CH, Park SB, Chiang JY, Lee CH, Choi HS.SourceNational Creative Research Initiatives Center for Nuclear Receptor Signals, Hormone Research Center, Gwangju, Republic of Korea.
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[Emergency care in patients with alcohol withdrawal delirium].

Batra A, Wernz FD.SourceSektion Suchtmedizin und Suchtforschung, Universitätsklinik für Psychiatrie und Psychotherapie, Calwer Str. 14, D-72076 Tübingen. anil.batra@med.uni-tuebingen.de
MMW Fortschritte der Medizin.MMW Fortschr Med.2013 Mar 7;155(4):51.
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Gamma aminobutyric acid (GABA) receptor agonists for acute stroke.

Liu J, Wang LN.SourceDepartment of Geriatric Neurology, Chinese PLA General Hospital, Beijing, China. Jason_liu1984@yahoo.cn.
The Cochrane database of systematic reviews.Cochrane Database Syst Rev.2013 Feb 28;2:CD009622. doi: 10.1002/14651858.CD009622.pub2.
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Japanese Journal

Chlormethiazole inhibition of cytochrome P450 2E1 as assessed by chlorzoxazone hydroxylation in humans

GEBHARDT AC
Hepatology 26, 957-961, 1997
NAID 30015134467

The effect of chlormethiazole on ischaemic neuronal damage in a model of transient focal ischaemia

SYDSERFF S. G.
Br J Pharmacol 114, 1631-1635, 1995
NAID 80008245401

The neuroprotective effect of chlormethiazole on ischaemic neuronal damage following permanent middle cerebral artery ischaemia in the rat

SYDSERFF SG
Neurodegeneration 4, 323-328, 1995
NAID 10012970200

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Clomethiazole
Systematic (IUPAC) name
	5-(2-Chloroethyl)-4-methyl-1,3-thiazole
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	POM (UK)
Routes	Oral
Identifiers
CAS number	533-45-9
ATC code	N05CM02
PubChem	CID 10783
ChemSpider	10327
UNII	0C5DBZ19HV
KEGG	D07330
ChEMBL	CHEMBL315795
Chemical data
Formula	C6H8ClNS
Mol. mass	161.653 g/mol
SMILES	eMolecules & PubChem
	InChI InChI=1S/C6H8ClNS/c1-5-6(2-3-7)9-4-8-5/h4H,2-3H2,1H3 ; Key:PCLITLDOTJTVDJ-UHFFFAOYSA-N ;
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