Clomethiazole
Pharmacology
Pharmacology
------------

Clomethiazole acts as a [positive allosteric modulator](/wiki/Allosteric_regulation "Allosteric regulation") at the [barbiturate](/wiki/Barbiturate "Barbiturate")/[picrotoxin](/wiki/Picrotoxin "Picrotoxin") site of the [GABAA](/wiki/GABAA_receptor "GABAA receptor") [receptor](/wiki/Receptor_%28biochemistry%29 "Receptor (biochemistry)"). It works to enhance the action of the [neurotransmitter](/wiki/Neurotransmitter "Neurotransmitter") [GABA](/wiki/Gamma-Aminobutyric_acid "Gamma-Aminobutyric acid") at this receptor. GABA is the major inhibitory neurotransmitter in the brain and produces anxiolytic, anticonvulsant, sedative, and hypnotic effects. Clomethiazole appears to also have another mechanism of action mediating some of its hypothermic and neuroprotective effects. The oxazole homologue is also knownUS Patent 3401172 4\-methyl\-5\-(beta\-chloroethyl)oxazole providing a little [QSAR](/wiki/QSAR "QSAR") information.

As opposed to barbiturates, clomethiazole doesn't affect the electrophysiological responses to excitatory aminoacids, and additionally, it also directly acts on chloride ion channels.

Clomethiazole is a potent [CYP2E1](/wiki/CYP2E1 "CYP2E1") enzyme inhibitor which slows down the metabolism of ethanol, hence its use in alcohol withdrawal. It is also an inhibitor of [CYP2B6](/wiki/CYP2B6 "CYP2B6") and possibly [CYP2A6](/wiki/CYP2A6 "CYP2A6") and thus can affect the plasma clearance of substrates of those enzymes.

When clomethiazole is administered via IV in addition to [carbamazepine](/wiki/Carbamazepine "Carbamazepine"), its clearance is increased by 30%, which results in a proportional reduction in plasma concentration. Therefore, when co\-administered with carbamazepine or other potent [CYP3A4](/wiki/CYP3A4 "CYP3A4") inducers via IV, it is necessary to increase the dose of clomethiazole.[Distraneurin 192mg: Summary of effects (In Croatian)](http://www.halmed.hr/upl/lijekovi/SPC/SPC_UP-I-530-09-17-02-642.pdf)


Are there other enzymes that clomethiazole inhibits?