Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than memantine by selectively inhibiting NMDA receptors

Yu Wei Liu, Chao Ying Li, Jia Lie Luo, Wen Ming Li, Hong Jun Fu, Yuan Zhi Lao, Li Jiang Liu, Yuan Ping Pang, Donald C. Chang, Zhi Wang Li, Robert W. Peoples, Yong Xun Ai, Yi Fan Han

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We have recently reported that bis(7)-tacrine could prevent glutamate-induced neuronal apoptosis through NMDA receptors. In this study, we demonstrated that in cultured rat cortical neurons, bis(7)-tacrine (IC50, 0.02 μM) prevented glutamate-induced excitotoxicity more substantially than memantine (IC50, 0.7 μM). In addition, bis(7)-tacrine was more efficient than memantine in buffering the intracellular Ca2+ triggered by glutamate. In cultured rat hippocampal neurons, bis(7)-tacrine inhibited 50 μM NMDA-activated current in a concentration-dependent manner with an IC50 of 0.68 ± 0.07 μM, which is five times more potent than that produced by memantine (IC50, 3.41 ± 0.36 μM; p < 0.05). By contrast, bis(7)-tacrine, up to 5 μM, did not significantly affect the current activated by 50 μM AMPA or 50 μM kainate. These results suggest that bis(7)-tacrine is more potent than memantine against glutamate-induced neurotoxicity by selectively inhibiting NMDA-activated current.

Original languageEnglish (US)
Pages (from-to)1007-1011
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume369
Issue number4
DOIs
StatePublished - May 16 2008

Keywords

  • Acetylcholinesterase inhibitor
  • Bis(7)-tacrine
  • Excitotoxicity
  • Glutamate receptor
  • Memantine
  • NMDA receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Liu, Y. W., Li, C. Y., Luo, J. L., Li, W. M., Fu, H. J., Lao, Y. Z., Liu, L. J., Pang, Y. P., Chang, D. C., Li, Z. W., Peoples, R. W., Ai, Y. X., & Han, Y. F. (2008). Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than memantine by selectively inhibiting NMDA receptors. Biochemical and Biophysical Research Communications, 369(4), 1007-1011. https://doi.org/10.1016/j.bbrc.2008.02.133