Possible Interaction: Chlormethiazole and Gamma-Aminobutyric Acid

“A low concentration of clomethiazole (30 micro M) also potentiated 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.”

“Both direct activation and gamma-aminobutyric acid potentiation are likely to contribute to the in vivo profile of clomethiazole.”

“ Chlormethiazole is a positive modulator of gamma-aminobutyric acid (GABA)(A) receptors used in the treatment of alcohol withdrawal seizures.”

“At an antiepileptic concentration (300 microM), chlormethiazole potentiated the action of exogenously applied GABA (1 mM) but did not affect responses to the glutamate receptor agonists N-methyl-D-aspartate (10 microM) or L-quisqualic acid (3 microM).”

“ Chlormethiazole positively modulates the gamma-aminobutyric acid (GABA)(A) receptor complex and is primarily used to treat certain life-threatening neurological events (e.g., refractory seizures and ethanol withdrawal syndrome).”

“ CMZ is known to potentiate 7-aminobutyric acid (GABAA) receptor function, a finding supported by the generalization to CMZ of the two benzodiazepines and phenobarbital.”

“Applied micro-iontophoretically, chlormethiazole was found to potentiate the inhibitory responses to GABA , muscimol and glycine, but not to acetylcholine.”

“These findings suggest that chlormethiazole may enhance GABA transmission beyond the GABA receptors, hypothetically at the level of the GABA receptor coupled ionophore (e.g. the chloride ion channel).”

“3 When applied with lower currents CMZ did not cause changes in firing rate, but enhanced the inhibitory effects of γ‐aminobutyric acid ( GABA ), muscimol and glycine in a dose‐dependent manner.”

“5 Intraperitoneal administration of CMZ (50–600 μmol kg−1) also enhanced responses to microiontophoretically applied GABA , muscimol and glycine.”