Inhibition of NMDA-gated ion channels by bis(7)-tacrine: whole-cell and single-channel studies

Neuropharmacology
Yu-Wei LiuChaoying Li

Abstract

Bis(7)-tacrine is a novel dimeric acetylcholinesterase inhibitor derived from tacrine, and has been proposed as a promising agent to treat Alzheimer's disease. We have recently reported that bis(7)-tacrine prevents glutamate-induced neuronal apoptosis by antagonizing NMDA receptors. The purpose of this study was to characterize bis(7)-tacrine inhibition of NMDA-activated current by using patch-clamp recording techniques. In cultured rat hippocampal neurons, bis(7)-tacrine inhibited NMDA-activated whole-cell current in a concentration-dependent manner with an IC(50) of 0.66+/-0.07 microM. Bis(7)-tacrine produced a gradual decline of NMDA-activated current to a steady-state, but this was not an indication of use-dependence. Also, the slow onset of inhibition by bis(7)-tacrine was not apparently due to an action at an intracellular site. Bis(7)-tacrine, 0.5 microM, decreased the maximal response to NMDA by 40% without changing its EC(50). Bis(7)-tacrine inhibition of NMDA-activated current was not voltage-dependent, and was independent of glycine concentration. Results of single-channel experiments obtained from cells expressing NR1 and NR2A subunits revealed that bis(7)-tacrine decreased the open probability and frequency of chan...Continue Reading

References

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Citations

Dec 29, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yuwei Liu, Chaoying Li
Jun 19, 2013·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yu-Wei LiuChao-Ying Li
Feb 15, 2012·Neuroscience Letters·Xi-Ji ShuYong-Xun Ai
Feb 15, 2015·Biochemical and Biophysical Research Communications·Yuwei LiuChao-Ying Li
May 31, 2019·Frontiers in Neuroscience·Dalinda Isabel Sánchez-VidañaYi-Fan Han

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