Benzodiazepine antagonists reduce epileptiform discharges in rat hippocampal slices.

Purpose: The antiepileptic effects of benzodiazepine-receptor (BZR) agonists have been well documented. Surprisingly, an antiepileptic effect for the BZR antagonist, flumazenil, has also been described, the mechanism of which is unknown. We investigated the effects of nanomolar concentrations of flumazenil and a structurally dissimilar BZR antagonist, propyl-beta-carboline-3-carboxylate (beta-CCP), on normal synaptic responses and epileptiform discharges induced by a variety of methods in the CA1 region of rat hippocampal slices.

Benzodiazepine antagonist flumazenil reduces hippocampal epileptiform activity.

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.

Involvement of endogenous benzodiazepine receptor ligands in brain disorders: therapeutic potential for benzodiazepine antagonists?

Many therapeutic effects of benzodiazepines are mediated by neuronal high-affinity binding sites, i.e. benzodiazepine receptors (BR), located on GABAA receptors.

Benzodiazepine antagonist flumazenil reduces bicuculline-induced enhancement of neuronal activity in the spinal cord.

The interaction between the GABAA receptor antagonist bicuculline and the benzodiazepine receptor (BR) antagonist flumazenil was studied in the lumbosacral cord of spinal cats. Bicuculline (0.8 mg/kg i.

Afferent stimulation frequency modulates GABAergic phenomena in the spinal cord: reversal by benzodiazepine antagonists.

Switching from a low (0.5 Hz) to a higher (5 Hz) frequency repetitive stimulation of hindlimb muscle nerve afferents reduced GABA-mediated dorsal root potentials and dorsal root reflexes in the lumbosacral cord of spinal cats. Benzodiazepine receptor antagonists flumazenil and Ro 15-3505 in a very low dose (0.