Chlormethiazole inhibits epileptiform activity by potentiating GABA A receptor function

• Published in: Brain research Vol. 884; no. 1; pp. 31 - 34
• Main Authors: Empson, Ruth M., Gee, Veronica J., Sheardown, Malcolm J., Newberry, Nigel R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 24.11.2000
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Bicuculline - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Chlormethiazole - pharmacology; Dose-Response Relationship, Drug; Epilepsy; Epilepsy - drug therapy; Epilepsy - metabolism; Epilepsy - physiopathology; GABA receptor; gamma-Aminobutyric Acid - metabolism; gamma-Aminobutyric Acid - pharmacology; Glutamate receptor; Male; N-Methylaspartate - pharmacology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; Quisqualic Acid - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - drug effects; Receptors, GABA-A - physiology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Stroke; Tetrodotoxin - pharmacology; Valine - analogs & derivatives; Valine - pharmacology; Disorders of the nervous system; GABA receptor; Stroke; Glutamate receptor; Epilepsy
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02875-4

Chlormethiazole has sedative, hypnotic, anticonvulsant and neuroprotective properties. Using in vitro grease-gap recordings, we show that it inhibits epileptiform activity in neocortical slices superfused with Mg 2+-free medium (IC 50∼200 μM). At an antiepileptic concentration (300 μM), 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 μM) or l-quisqualic acid (3 μM). The GABA A receptor antagonist N-methyl-bicuculline (50 μM) reduced chlormethiazole’s potency to inhibit the epileptiform activity. These results indicate that chlormethiazole’s anticonvulsant action is likely mediated by potentiating GABA Aergic inhibition rather than by antagonising glutamatergic excitation.