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

Eur J Pharmacol. 1987 Jun 12;138(1):133-6. doi: 10.1016/0014-2999(87)90349-9.

Abstract

(-)-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / toxicity
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Female
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • N-Methylaspartate
  • Naloxone / pharmacology*
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / enzymology
  • Oxadiazoles / toxicity
  • Pregnancy
  • Quisqualic Acid
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / physiology*

Substances

  • Oxadiazoles
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Aspartic Acid
  • Naloxone
  • N-Methylaspartate
  • Quisqualic Acid
  • L-Lactate Dehydrogenase