Title:N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and their
Pharmacological Implication: A Medicinal Chemistry-oriented
Perspective Outline
Volume: 31
Issue: 29
关键词:
N -甲基- D -天冬氨酸受体拮抗剂，阿尔茨海默病，药理意义，嗜离子性谷氨酸受体，中风，癫痫。
摘要: 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.
