Clomethiazole

Chlormethiazole is an potent and orally active GABAA agonist[1]. Chlormethiazole inhibits cytochrome P450 isoforms: CYP2A6 and CYP2E1 in human liver microsomes. Chlormethiazole is an anticonvulsant agent and has the potential for treating convulsive status epilepticus[2].

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

Clomethiazole (1 mM), in the absence of GABA, to α1/β1/γ2 or α1/β2/γ2 subunit-containing cells produced large whole-cell currents[1]. Clomethiazole activate GABAA currents in α1/β1/γ2- and α1/β2/γ2-containing cells, with EC50 values of 0.3 and 1.5 mM, respectively[1]. Clomethiazole (30 μM) at low concentration also potentiates the action of GABA in both cell types, equivalent to a 3-fold increase in potency and up to 1.8-fold increase in maximal current[1]. Clomethiazole inhibits cytochrome P450 isoforms, CYP2A6 and CYP2E1 with IC50 values of 24 µM and 42 µM, respectively, in human liver microsomes, meanwhile all other isoforms exhibiting values > 300 µM[2].

[1]. Nelson RM, et al.Electrophysiological actions of gamma-aminobutyric acid and clomethiazole on recombinant GABA(A) receptors.Eur J Pharmacol. 2002 Oct 11;452(3):255-62.

[2]. Stresser DM, et al. Selective Time- and NADPH-Dependent Inhibition of Human CYP2E1 by Clomethiazole.Drug Metab Dispos. 2016 Aug;44(8):1424-30

DATA ITEMS CITED :

3

MOLECULAR FORMULA :

C6-H8-Cl-N-S

MOLECULAR WEIGHT :

161.66

WISWESSER LINE NOTATION :

T5N CSJ D2G E1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2110 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 7,167,1964

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

190 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

APSXAS Acta Pharmaceutica Suecica. (Apotekarsocieteten-Farmacevtiska Foereningen, Box 1136, S-111, 81 Stockholm, Sweden) V.1- 1964- Volume(issue)/page/year: 8,39,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

94 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

APSXAS Acta Pharmaceutica Suecica. (Apotekarsocieteten-Farmacevtiska Foereningen, Box 1136, S-111, 81 Stockholm, Sweden) V.1- 1964- Volume(issue)/page/year: 7,423,1970