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  • Title: Benzodiazepine antagonist flumazenil reduces hippocampal epileptiform activity.
    Author: Polc P, Jahromi SS, Facciponte G, Pelletier MR, Zhang L, Carlen PL.
    Journal: Neuroreport; 1995 Jul 31; 6(11):1549-52. PubMed ID: 7579146.
    Abstract:
    We examined the effects of the benzodiazepine antagonist, flumazenil, on epileptiform discharges evoked in the hippocampal CA1 region in vitro. Application of 100 nM flumazenil did not affect normal synaptic responses; however, flumazenil did depress epileptiform discharges induced by 8 mM [K+]o. Epileptiform discharges induced by the GABAA channel antagonist picrotoxin or by the K+ channel blocker 4-aminopyridine were unaffected. Application of the high-affinity, low-efficacy benzodiazepine partial inverse agonist, Ro 19-4603, blocked the anticonvulsant effect of flumazenil, indicating that this action of flumazenil is mediated at a benzodiazepine binding site located on the GABAA receptor. A likely explanation of the present results is that flumazenil antagonizes the action of an endogenous benzodiazepine inverse agonist, which is released during epileptiform discharges evoked in high K+ ACSF.
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