Neuroprotective action of a novel compound-M50463-in primary cultured neurons

The neuroprotective effects of a novel synthetic compound, M50463, have bee n determined by using embryonic rat neocortical neurons in various culture conditions. M50463 was initially characterized as a potent specific ligand for a voltage-dependent sodium channel by radioligand binding studies. In f act, M50463 inhibited neuronal cell death induced by veratrine and inhibite d an increase of the intracellular calcium level in neurons evoked by verat rine. In addition to such expected effects, M50463 had the ability to preve nt glutamate neurotoxicity, to promote the neuronal survival in serum-depri ved medium and to prevent nitric oxide-induced neurotoxicity. These results suggested that M50463 is not a simple sodium channel blocker, but a neurop rotective agent which has some crucial mechanism of action on neuronal deat h occurring in various situations, and it is a novel, innovative candidate for neuroprotective therapy for various neurodegenerative disorders. (C) 19 99 Elsevier Science B.V. All rights reserved.