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.
Malgouris
C
C
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry-sur-Seine, France.
Daniel
M
M
Doble
A
A
D000818:Animals; D016923:Cell Death; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000032:analysis; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D019782:Riluzole; D015222:Sodium Channels / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology*; D014701:Veratridine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D013844:Thiazoles; D010566:Virulence Factors, Bordetella; D016202:N-Methylaspartate; D014701:Veratridine; D019782:Riluzole; D007770:L-Lactate Dehydrogenase; D037342:Pertussis Toxin