title: Benzodiazepine antagonist flumazenil reduces hippocampal epileptiform activity.
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.
authors.affiliation: Department of Medicine (Neurology), Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Polc
authors.forename: S S
authors.initials: SS
authors.lastname: Jahromi
authors.forename: G
authors.initials: G
authors.lastname: Facciponte
authors.forename: M R
authors.initials: MR
authors.lastname: Pelletier
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: P L
authors.initials: PL
authors.lastname: Carlen
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008832:Microchemistry; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D005442:Flumazenil; D011188:Potassium