Valnoctamide enhances phasic inhibition: A potential target mechanism for the treatment of benzodiazepine‐refractory status epilepticus

Summary Valnoctamide ( VCD ), a derivative of valproate, suppresses electrographic seizures in animal models of status epilepticus ( SE ), even when the seizures are resistant to benzodiazepines ( BZD s). We therefore tested the effect of VCD on miniature inhibitory postsynaptic currents (m IPSC s) in CA 1 pyramidal cells to determine if VCD acts directly on γ‐aminobutyric acid ( GABA) A receptors. Bath‐applied VCD induced a specific, rapid, dose‐dependent, and reversible slowing of the decay of m IPSC s (i.e., increased time constant) with no effect on their frequency or amplitude. This is similar to the effect of BZD s on m IPSC s, but the effect of VCD persisted in the presence of the BZD ‐binding site antagonist flumazenil, and was additive to the effect of the BZD , diazepam. These data suggest that VCD acts through a different binding site than that of BZD s, which likely accounts for its effect on BZD ‐refractory SE . A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .