Chlormethiazole

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. 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, 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. 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. The oxazole homologue is also known providing a little QSAR information.