Uses
Clomethiazolum is a drug which is structurally related to thiamine (vitamin B1) but acts like a sedative, hypnotic, muscle relaxant and anticonvulsant.
Definition
ChEBI: 5-(2-chloroethyl)-4-methylthiazole is a member of thiazoles.
brand name
Clomiazin;Distraneurine;Emineurina;Gebriazol;Hemineurine;Heminevrin;Somnevrin.
World Health Organization (WHO)
Clomethiazole, which has sedative, anxiolytic and anticonvulsant
activity, was introduced in 1960 for the treatment of acute alcohol withdrawal,
delirium tremens, status epilepticus, eclamptic toxaemia, sleep disturbances in the
elderly and agitation in psychogeriatic patients. It is also used as a sedative in
certain anaesthetic procedures. There is little evidence of primary dependence in
man but secondary dependence can occur in patients with a history of abuse of
other substances, particularly alcohol. Dependence of this type has been reported
as a result of inappropriate, long-term prescribing to outpatient alcoholics.
Clomethiazole should not be prescribed to alcoholics who continue to drink.
Adverse interactions with alcohol have been fatal. Although not controlled under
the 1971 Convention on Psychotropic Substances, clomethiazole is subject to
analogous controls in some countries.
Biological Activity
Sedative and anticonvulsant which is neuroprotective in a number of animal models. Prevents the degeneration of serotonergic nerve terminals induced by MDMA ('Ecstasy').
Synthesis
The general procedure for the synthesis of 5-(2-chloroethyl)-4-methylthiazole from 4-methyl-5-hydroxyethylthiazole was as follows: referring to Example 18, 2-(4-methylthiazol-5-yl)ethanol (500 mg, 3.49 mmol) was dissolved in thionyl chloride (4 mL). The reaction mixture was stirred under reflux conditions for 3 hours. After completion of the reaction, the mixture was concentrated to dryness to give a light yellow solid product (680 mg, yield: 98%). The product was analyzed by ESI-MS and showed m/z: 162.0 [M + H]+.
References
[1] Patent: US2017/158680, 2017, A1. Location in patent: Paragraph 0385
[2] Journal of the American Chemical Society, 2001, vol. 123, # 6, p. 1017 - 1022
[3] Pharmaceutical Chemistry Journal, 1999, vol. 33, # 12, p. 658 - 660
[4] Journal of the American Chemical Society, 1982, vol. 104, # 18, p. 4934 - 4943
[5] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 22, p. 5988 - 6003
