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

doi:10.1016/j.bbrc.2008.02.133

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

11 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 language	English (US)
Pages (from-to)	1007-1011
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	369
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.02.133
State	Published - 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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10.1016/j.bbrc.2008.02.133

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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

Liu, YW, Li, CY, Luo, JL, Li, WM, Fu, HJ, Lao, YZ, Liu, LJ, Pang, YP, Chang, DC, Li, ZW, Peoples, RW, Ai, YX & Han, YF 2008, 'Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than memantine by selectively inhibiting NMDA receptors', Biochemical and Biophysical Research Communications, vol. 369, no. 4, pp. 1007-1011. https://doi.org/10.1016/j.bbrc.2008.02.133

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

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.",

keywords = "Acetylcholinesterase inhibitor, Bis(7)-tacrine, Excitotoxicity, Glutamate receptor, Memantine, NMDA receptor",

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

note = "Funding Information: This work was supported by the grants from the Research Grants Committee of Hong Kong (HKUST 6133/03M and 6441/06M) and the Grant 2006AB190 from the Natural Science Foundation of Hubei Province, China.",

year = "2008",

month = may,

day = "16",

doi = "10.1016/j.bbrc.2008.02.133",

language = "English (US)",

volume = "369",

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T1 - Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than memantine by selectively inhibiting NMDA receptors

AU - Liu, Yu Wei

AU - Li, Chao Ying

AU - Luo, Jia Lie

AU - Li, Wen Ming

AU - Fu, Hong Jun

AU - Lao, Yuan Zhi

AU - Liu, Li Jiang

AU - Pang, Yuan Ping

AU - Chang, Donald C.

AU - Li, Zhi Wang

AU - Peoples, Robert W.

AU - Ai, Yong Xun

AU - Han, Yi Fan

N1 - Funding Information: This work was supported by the grants from the Research Grants Committee of Hong Kong (HKUST 6133/03M and 6441/06M) and the Grant 2006AB190 from the Natural Science Foundation of Hubei Province, China.

PY - 2008/5/16

Y1 - 2008/5/16

N2 - 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.

AB - 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.

KW - Acetylcholinesterase inhibitor

KW - Bis(7)-tacrine

KW - Excitotoxicity

KW - Glutamate receptor

KW - Memantine

KW - NMDA receptor

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ER -

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

Abstract

Keywords

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