Chlormethiazole inhibits epileptiform activity by potentiating GABAA receptor function

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 Mg2+-free medium (IC(50)similar to 200 muM). At an antiepileptic concentration (300 muM), 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 muM) or L-quisqualic acid (3 muM). The GABA, receptor antagonist N-methylbicuculline (50 muM) reduced chlormethiazole's potency to inhibit the epileptiform activity. These results indicate that chlormethiazole's anticonvulsant action is likely mediated by potentiating GABA(A)ergic inhibition rather than by antagonising glutamatergic excitation. (C) 2000 Elsevier Science B.V. All rights reserved.