High concentrations of naloxone attenuate N-methyl-D-aspartate receptor-mediated neurotoxicity

(-)-Naloxone, 1 mM, partially reduced neuronal loss induced by exposure of murine cortical cell cultures to N-methyl-D-aspartate (NMDA) or quinolinate, but produced little or no attenuation of kainate or quisqualate neurotoxicity. Antagonism of NMDA neurotoxicity was (-)-naloxone concentration-dependent between 100 μM and 3 mM. (+)-Naloxone produced a slightly greater reduction of NMDA neurotoxicity, arguing against mediation by opioid receptors. Although this novel neuron-protective action of (-)-naloxone was weak, it may contribute to reported beneficial effects in CNS ischemia.