APPARENT INDEPENDENT ACTION OF NIMODIPINE AND GLUTAMATE ANTAGONISTS TO PROTECT CULTURED NEURONS AGAINST GLUTAMATE-INDUCED DAMAGE

A disturbed cellular calcium homeostasis is suggested to play a pivota l role in neuronal damage. Energy deficiency causes depolarization of the neuronal membrane and Ca2+ enters the cells through different ion channels, the voltage-sensitive L-type Ca2+ channels and the NMDA-oper ated channels being the main gates. In the present study we used prima ry cultures of rat hippocampal neurons to demonstrate that the dihydro pyridine calcium antagonist nimodipine, the non-competitive NMDA antag onists dizocilpine and memantine, as well as the AMPA antagonist NBQX ihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), attenuate the gluta mate-induced neuronal damage dose-dependently. Nimodipine applied simu ltaneously with NMDA-antagonists and NBQX, respectively, resulted in s omewhat greater neuroprotection of glutamate-treated neurons compared with the effects of these agents applied singly. The type of interacti on is best described by an independent action in combination, which me ans that the relative effects of nimodipine were not enhanced. Therefo re, it can be considered as a lack of potentiation. (C) 1997 Elsevier Science Ltd.