Clomethiazole structure.svg
Clomethiazole ball-and-stick model.png
Clinical data
AHFS/ International Drug Names
Routes of
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life 3.6–5 hours
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.788 Edit this at Wikidata
Chemical and physical data
Formula C6H8ClNS
Molar mass 161.653 g/mol g·mol−1
3D model (JSmol)
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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, having the same mechanism of action as traditional barbiturates. It is also rarely used for the management of agitation, restlessness, short-term insomnia and Parkinson’s disease in the elderly, when all other treatment options have failed. In the UK, it is sold under the brand Heminevrin (AstraZeneca Pharmaceuticals). Other brand names include Nevrin in Romania, Distraneurin in Germany and Distraneurine in Spain. The drug is marketed either as a free base in an oily solution containing 192 mg in capsule form, or as clomethiazole edisylate syrup. Due to its high toxicity compared to similar drugs it is not recommended as a first-line treatment for any indication and is particularly dangerous to patients with an elevated risk for drug abuse such as those with a personal or familial history of addiction.


Clomethiazole acts as a positive allosteric modulator at the barbiturate/picrotoxin site of the GABAA receptor. It works to enhance the action of the neurotransmitter GABA at this receptor.[2] 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.[2] The oxazole homologue is also known[3] providing a little QSAR information.

Adverse effects[edit]

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.[4]


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.[5]

Due to clomethiazole’s action at the barbiturate complex the benzodiazepine antidote flumazenil cannot reverse the effects of overdose; overdose treatment is restricted to the application of a mechanical ventilation apparatus until enough of the drug has been metabolized and/or excreted for the patient to breathe sufficiently without assistance. As with all GABAA agonists/allosteric agonists chomethiazole has a high potential for misuse and abuse, and intentional overdoses have been documented.

Drummer Keith Moon of the rock band The Who died of a clomethiazole overdose.[6]

See also[edit]


  1. ^
    ‹See Tfd›CH patent 200248, ”Verfahren zur Darstellung von 4-Methyl-5-B-chloräthylthiazol”, issued 1938-09-30, assigned to Hoffmann-La Roche 
  2. ^ a b “Clomethiazole – an overview – ScienceDirect Topics”.
  3. ^ US Patent 3401172 4-methyl-5-(beta-chloroethyl)oxazole
  4. ^ Reilly, T. M. (1976). “Physiological dependence on, and symptoms of withdrawal from, chlormethiazole”. The British Journal of Psychiatry. 128 (4): 375–378. doi:10.1192/bjp.128.4.375. PMID 1260235.
  5. ^ 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.
  6. ^ 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.