Opioids and non-opioid enantiomers selectively attenuate N-methyl-D-aspartate neurotoxicity on cortical neurons

摘要: Abstract Addition of 1 μM-1 mM methadone to the bathing medium produced a concentration-dependent reduction in neurotoxicity exogenously applied N-methyl-D-aspartate (NMDA) murine cortical cell culture (EC50 about 100 μM); persisted at intense NMDA exposure, consistent with non-competitive inhibition. Methadone also protected against exposure quinolinate but not quisqualate or kainate. Concentrations (100 μM-3 mM) several other opioids - morphine, fentanyl, codeine, meperidine, dextropropoxyphene, and naltrexone were additionally found produce reductions neurotoxicity. This novel neuron-protective effect was mediated by conventional opioid receptors: non-opioid enantiomer morphine exhibited potency equal greater than that enantiomer, naloxone did act as an antagonist. The possibility opioids, especially enantiomers might provide useful therapeutic approach diseases states involving receptor-mediated neurotoxicity, warrants further study.