関: chlormethiazole

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/12 19:57:35」(JST)

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

It 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 UK, it is sold under the brand Heminevrin (AstraZeneca Pharmaceuticals). Another brand name includes Nevrin in Romania, Distraneurin in Germany and Distraneurine in Spain. The drug is marketed either as a free base in an oily suspension containing 192 mg in capsule form, or as clomethiazole edisylate syrup. Clomethiazole is currently not approved by the FDA for use in the United States in any form, and thus is not available for medical use.

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. Alcohol multiplies the effect. As the drug can be fatal in high doses, prescribing clomethiazole outside a controlled environment, like a hospital, is not recommended, especially because there are much less toxic alternatives, such as diazepam. Diazepam is one of many drugs belonging to the benzodiazepine class, with a long half-life (50–100 hours) and a very low risk of fatal overdose, as long as the patient does not consume alcohol or certain other types of medication.^[3]

Drummer Keith Moon of rock band The Who died of a clomethiazole overdose.^[4]

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
^ Springer, Mike (2013-05-20). "Keith Moon's Last Interview, 1978". Retrieved 2014-10-11. An autopsy showed that Moon had taken 32 tablets of Clomethiazole. His doctor had told him not to exceed three per day.

English Journal

Oral clomethiazole treatment for paediatric non-convulsive status epilepticus.

Das D1, Varadkar S2, Das KB3.
Epileptic disorders : international epilepsy journal with videotape.Epileptic Disord.2016 Mar 1;18(1):87-91. doi: 10.1684/epd.2016.0795.
We report a retrospective case study of the use of clomethiazole for treatment of non-convulsive status epilepticus in a patient not responding to benzodiazepines, illustrated by EEG and video. Clomethiazole can be considered as a safe oral option for management of non-convulsive status epilepticus
PMID 26842397

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project.

Huerta C1, Abbing-Karahagopian V2, Requena G3, Oliva B1, Alvarez Y4, Gardarsdottir H2,5, Miret M6, Schneider C7, Gil M1, Souverein PC2, De Bruin ML2, Slattery J4, De Groot MC2, Hesse U8, Rottenkolber M9, Schmiedl S10,11, Montero D1, Bate A12, Ruigomez A13, García-Rodríguez LA13, Johansson S14, de Vries F2,15,16, Schlienger RG17, Reynolds RF18, Klungel OH2,19, de Abajo FJ3,20.
Pharmacoepidemiology and drug safety.Pharmacoepidemiol Drug Saf.2016 Mar;25 Suppl 1:56-65. doi: 10.1002/pds.3825. Epub 2015 Jul 7.
PURPOSE: Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare da
PMID 26149383

Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

Jochum T1, Hoyme J1, Schulz S2, Weißenfels M1, Voss A2, Bär KJ3.
Drug and alcohol dependence.Drug Alcohol Depend.2016 Feb 1;159:142-51. doi: 10.1016/j.drugalcdep.2015.12.030. Epub 2016 Jan 4.
BACKGROUND: Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function.METHODS: Thirty ma
PMID 26790823

Japanese Journal

第I相試験日欧同時実施の経験脳卒中治療薬Clomethiazoleの24時間静注試験

板橋明,坪井實,中道昇,小代隆三
臨床薬理 34(1), 195, 2003-01-31
NAID 10011422487

Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I) : final results

LYDEN P
Stroke 33, 122-128, 2002
NAID 30022679290

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リンク元	「chlormethiazole」「クロメチアゾール」

「chlormethiazole」

Clomethiazole
Systematic (IUPAC) name
	5-(2-Chloroethyl)-4-methyl-1,3-thiazole
Clinical data
AHFS/Drugs.com	International Drug Names
Legal status	UK: POM;
Routes	Oral
Pharmacokinetic data
Half-life	3.6 - 5 hours
Identifiers
CAS number	533-45-9
ATC code	N05CM02
PubChem	CID 10783
ChemSpider	10327
UNII	0C5DBZ19HV
KEGG	D07330
ChEMBL	CHEMBL315795
Chemical data
Formula	C6H8ClNS
Molecular mass	161.653 g/mol
	SMILES ClCCC1=C(C)N=CS1;
	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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