In vivo evidence for functional NMDA receptor blockade by memantine in rat hippocampal neurons

Viktor Szegedi, Gábor Juhász, Chris G. Parsons, Dénes Budai

Research output: Contribution to journalArticle

9 Citations (Scopus)


Antagonising the NMDA (N-methyl-d-aspartate) receptor complex is a widely hypothesised therapeutic approach in several neurodegenerative conditions, such as Alzheimer's disease. Memantine, a moderate affinity uncompetitive NMDA receptor antagonist, has been in clinical use for several years and numerous experimental data support its NMDA receptor blocking effects. It has recently been reported in transfected HEK293T cells that physiological concentrations of Mg2+ may impart partial NMDA receptor subtype selectivity and weaken the overall inhibitory actions of memantine in NMDA receptor-mediated cellular events. In the present study, we set out to investigate the effect of intravenously applied memantine on iontophoresed NMDA-evoked firing of hippocampal CA1 neurons using in vivo conditions. Cumulative doses of memantine in the rat (4, 8 and 16 mg/kg i.v.) caused the firing rate to decrease in a dose-dependent manner to 77 ± 7, 58 ± 8 and 34 ± 12% of control, respectively, while saline application had no significant effect. We show that therapeutic doses of memantine are able to antagonize NMDA receptor-mediated activity in the principal cells of the hippocampus in vivo, i.e. in the presence of physiological concentrations of Mg2+.

Original languageEnglish
Pages (from-to)1189-1194
Number of pages6
JournalJournal of neural transmission
Issue number10
Publication statusPublished - Oct 1 2010


  • Alzheimer's disease
  • Antagonist
  • NMDA receptor
  • Single-unit

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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