The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1.

Riluzole is believed to exert its anticonvulsant and neuroprotective actions by reducing glutamate release. This study demonstrated that 10-30 microM riluzole reduces the K(+)-evoked release of glutamate and aspartate from slices of hippocampal area CA1. Only higher concentrations reduced gamma-aminobutyrate (GABA) release. These actions of riluzole were not occluded by tetrodotoxin. Riluzole did not diminish the ability of glutamate analogues to depolarize CA1 pyramidal cells, as determined from grease-gap recordings. Therefore the anticonvulsant and neuroprotective actions of riluzole in the hippocampus may be at least partly explained by its ability to inhibit glutamate/aspartate release from synaptic terminals.