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 microM 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.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D016202:N-Methylaspartate; D009270:Naloxone / Q000494:pharmacology*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology; D010069:Oxadiazoles / Q000633:toxicity; D011247:Pregnancy; D016318:Quisqualic Acid; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D010069:Oxadiazoles; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D009270:Naloxone; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D007770:L-Lactate Dehydrogenase