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Glutamate Binding-Site Ligands of NMDA Receptors

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Excitatory neurotransmission mediated by NMDA (N-methyl-D-aspartic acid) receptors plays a key role in both healthy and diseased processes in the brain. Therefore, bioactive compounds that can interact selectively with these receptors have been the aim of extensive research in the search of effective therapeutic agents or, at least, useful pharmacological tools. NMDA receptors are heteromeric ion channels that contain different modulatory sites capable to bind subunit-selective ligands. In particular, the activation of NMDA receptors requires two distinct ligands: glutamate (the endogenous agonist) and glycine (the co-agonist). In view of the renewed interest in this research area and the high therapeutic potential of this target, this review presents an updated survey of ligands which interact with the glutamate binding-site of the NMDA receptors, their rational development, and data on the structure-activity relationship which are of utmost importance for the design of novel lead compounds.

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Keywords: (N-methyl-D-aspartic acid); Glutamate; NMDA receptors; competitive agonists; competitive antagonists; endogenous; neuropathological; neurotransmission; pharmacological; tetrameric

Document Type: Research Article

Publication date: 2011-12-01

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