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


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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.

Об авторах

Vikas Rana

Department of Pharmacy, Graphic Era Hill University

Email: info@benthamscience.net

Shayantan Ghosh

Department of Pharmacy, Graphic Era Hill University

Email: info@benthamscience.net

Akanksha Bhatt

Department of Pharmacy, Graphic Era Hill University

Email: info@benthamscience.net

Damini Bisht

Department of Pharmacy, Graphic Era Hill University

Email: info@benthamscience.net

Gaurav Joshi

Department of Pharmaceutical Sciences, Hemvati Nandan Bahuguna Garhwal University (A Central University)

Email: info@benthamscience.net

Priyank Purohit

Department of Pharmacy, Graphic Era Hill University

Автор, ответственный за переписку.
Email: info@benthamscience.net

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