NMDA receptor-mediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine

Michael Weller, Françoise Finiels-Marlier, Steven M. Paul

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Effects of amantadine and memantine on NMDA receptor-mediated glutamate toxicity were studied in cultured cerebellar, cortical and mesencephalic neurons. Both drugs protected cerebellar and cortical neurons against glutamate toxicity, memantine being consistently more effective than amantadine but less effective than MK-801. Glutamate toxicity of dopaminergic neurons in mesencephalic cultures was only mildly attenuated by memantine but was also only incompletely blocked by MK-801. These findings suggest that adamantanamines act by inhibiting NMDA receptor-mediated excitatory neurotransmission. However, since non-NMDA receptors appear to be principal mediators of glutamate toxicity of dopaminergic mesencephalic neurons, adamantanamines may fail to protect the nigrostriatal neurons which specifically degenerate in Parkinson's disease.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalBrain Research
Volume613
Issue number1
DOIs
StatePublished - Jun 4 1993

Keywords

  • Amantadine
  • Excitotoxicity
  • Glutamate
  • Memantine
  • N-methyl-d-amphetamine neuron
  • Neurotoxicity

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