N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and their
Pharmacological Implication: A Medicinal Chemistry-oriented
Perspective Outline

Vikas      Rana; Shayantan      Ghosh; Akanksha      Bhatt; Damini      Bisht; Gaurav      Joshi; Priyank      Purohit
doi:10.2174/0109298673288031240405061759
Abstract

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc.). Additionally, reported NMDA antagonists from different sources, such as synthetic, semisynthetic, and natural resources, are explained by their mechanism of action and pharmacological role. The comprehensive report also addresses the chemical spacing of NMDA inhibitors and in-vivo and in-vitro models to test NMDA antagonists. Since the Blood-Brain Barrier (BBB) is the primary membrane that prevents the penetration of a wide variety of drug molecules, we also elaborate on the medicinal chemistry approach to improve the effectiveness of their antagonists.
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DOI https://dx.doi.org/10.2174/0109298673288031240405061759	Print ISSN 0929-8673
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Current Medicinal Chemistry

N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and their Pharmacological Implication: A Medicinal Chemistry-oriented Perspective Outline

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