NMDA Receptor Antagonists: Repositioning of Memantine as a Multitargeting Agent for Alzheimer's Therapy

Md Tanvir Kabir; Mohammad A Sufian; Md Sahab Uddin; Mst Marium Begum; Shammi Akhter; Ariful Islam; Bijo Mathew; Md Siddiqul Islam; Md Shah Amran; Ghulam Md Ashraf

doi:10.2174/1381612825666191011102444

NMDA Receptor Antagonists: Repositioning of Memantine as a Multitargeting Agent for Alzheimer's Therapy

Curr Pharm Des. 2019;25(33):3506-3518. doi: 10.2174/1381612825666191011102444.

Authors

Md Tanvir Kabir¹, Mohammad A Sufian², Md Sahab Uddin^{3

4}, Mst Marium Begum², Shammi Akhter³, Ariful Islam⁵, Bijo Mathew⁶, Md Siddiqul Islam³, Md Shah Amran⁷, Ghulam Md Ashraf^{8

9}

Affiliations

¹ Department of Pharmacy, BRAC University, Dhaka, Bangladesh.
² Department of Pharmacy, East West University, Dhaka, Bangladesh.
³ Department of Pharmacy, Southeast University, Dhaka, Bangladesh.
⁴ Pharmakon Neuroscience Research Network, Dhaka, Bangladesh.
⁵ Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, United States.
⁶ Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad, India.
⁷ Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, Bangladesh.
⁸ King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
⁹ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

PMID: 31604413
DOI: 10.2174/1381612825666191011102444

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes problems with memory, thinking, and behavior. Currently, there is no drug that can reduce the pathological events of this degenerative disease but symptomatic relief is possible that can abate the disease condition. N-methyl-D-aspartate (NMDA) receptors exert a critical role for synaptic plasticity as well as transmission. Overstimulation of glutamate receptors, predominantly NMDA type, may cause excitotoxic effects on neurons and is recommended as a mechanism for neurodegeneration. Atypical activation of the NMDA receptor has been suggested for AD by synaptic dysfunction. NMDA receptor antagonists especially memantine block the NMDA receptor and can reduce the influx of calcium (Ca2+) ions into neuron, thus, toxic intracellular events are not activated. This review represents the role of NMDA receptors antagonists as potential therapeutic agents to reduce AD. Moreover, this review highlights the repositioning of memantine as a potential novel therapeutic multitargeting agent for AD.

Keywords: Alzheimer’s disease; NMDA antagonists; amyloid beta; glutamate receptors; memantine; tau..

Publication types

Review

MeSH terms

Alzheimer Disease / drug therapy*
Drug Repositioning
Humans
Memantine / therapeutic use*
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

Receptors, N-Methyl-D-Aspartate
Memantine