N-Methyl-D-aspartate receptor antagonists have variable affect in 3-nitropropionic acid toxicity

Payman Nasr, Timothy Carbery, James W. Geddes

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


There is accumulating evidence that excitotoxicity and oxidative stress resulting from excessive activation of glutamate (N-methyl-d-aspartate) NMDA receptors are major participants in striatal degeneration associated with 3-nitropropionic acid (3NP) administration. Although excitotoxic and oxidative mechanisms are implicated in 3NP toxicity, there are conflicting reports as to whether NMDA receptor antagonists attenuate or exacerbate the 3NP-induced neurodegeneration. In the present study, we investigated the involvement of NMDA receptors in striatal degeneration, protein oxidation and motor impairment following systemic 3NP administration. We examined whether NMDA receptor antagonists, memantine and ifenprodil, influence the neurotoxicity of 3NP. The development of striatal lesion and protein oxidation following 3NP administration is delayed by memantine but not affected by ifenprodil. However, in behavioral experiments, memantine failed to improve and ifenprodil exacerbated the motor deficits associated with 3NP toxicity. Together, these findings suggest caution in the application of NMDA receptor antagonists as a neuroprotective agent in neurodegenerative disorders associated with metabolic impairment.

Original languageEnglish
Pages (from-to)490-498
Number of pages9
JournalNeurochemical Research
Issue number3
StatePublished - Mar 2009


  • 3-Nitropropionic acid
  • Excitotoxicity
  • Ifenprodil
  • MK-801
  • Memantine
  • Metabolic impairment
  • N-Methyl-d-aspartate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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