Clomethiazole

Not to be confused with Clotrimazole.

Clomethiazole

Systematic (IUPAC) name
5-(2-Chloroethyl)-4-methyl-1,3-thiazole
Clinical data
AHFS/Drugs.com	International Drug Names
Legal status	UK: POM (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Biological half-life	3.6–5 hours
Identifiers
CAS Number	533-45-9 N
ATC code	N05CM02 (WHO)
PubChem	CID: 10783
ChemSpider	10327 Y
UNII	0C5DBZ19HV Y
KEGG	D07330 Y
ChEMBL	CHEMBL315795 Y
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 Y Key:PCLITLDOTJTVDJ-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Clomethiazole (also called chlormethiazole) is a sedative and hypnotic originally developed by Hoffmann-La Roche in the 1930s. 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.

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. 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.

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.

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.

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