Neuroprotective effects of riluzole on N-methyl-D-aspartate- or veratridine-induced neurotoxicity in rat hippocampal slices.

The neuroprotective activity of riluzole has been studied on N-methyl-D-aspartate (NMDA)- or veratridine-induced toxicity in immature rat hippocampal slices. Neurodegeneration was assessed by the measurement of LDH release and histology. Veratridine-induced LDH release can be inhibited by 100 microM riluzole (-90% and by tetrodotoxin (1 microM). Riluzole markedly reduced (-59%) the NMDA-induced LDH release and this protective effect was confirmed by histology. Riluzole inhibited the NMDA-induced LDH release in the presence of tetrodotoxin. Moreover, a pretreatment with pertussis toxin (1 microgram/ml) abolished the effect of riluzole against NMDA-induced neurotoxicity. These results support the view that the neuroprotective properties of riluzole could be exerted via two distinct mechanisms of action.