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A Promising Dual-functional Neuroprotective Derivative of Memantine

Xiaoyong Jin, Zheng Liu, Baojian Guo, Gaoxiao Zhang, Zaijun Zhang, Lipeng Xu, Yuqiang Wang, Yewei Sun

Abstract


Background Memantine, an open-channel, uncompetitive blocker of NMDA receptors, is a major treatment for moderate-to-severe Alzheimer’s disease. The NMDA receptor activity can also be inhibited allosterically by S-nitrosylation of Cys residues, a redox-mediated chemical reaction.

Aim To enhance the inhibitory effect of memantine on NMDA receptors and its neuroprotective
effect.

Settings and Design In this study, we designed and synthesized a memantine nitrate compound (MN-2, also known as YQW-035), with the potential for both allosteric and direct uncompetitive blockade. Then, the protective effects of MN-2 were evaluated both in vitro and in vivo.

Results and Conclusions Biological evaluations demonstrated that MN-2 showed a stronger protective effect in cultured neuronal cells and in a rat transient stroke model compared with memantine. The mechanism underlying the action of MN-2 may be attributed to its dual inhibition of NMDA receptors. These results suggested MN-2 has promising potential for treatment of various neurological disorders characterized by overstimulation of NMDA receptors.


Keywords


memantine nitrate, neurological disorder, NMDA receptor, S-nitrosylation

Full Text:

References


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