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NMDAR PAMs: Multiple Chemotypes for Multiple Binding Sites.

Paul J Goldsmith1

  • 1Eli Lilly and Co. Ltd, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, United Kingdom.

Current Topics in Medicinal Chemistry
|October 30, 2019
PubMed
Summary
This summary is machine-generated.

N-methyl-D-aspartate receptors (NMDARs) are vital for brain function. This review explores positive allosteric modulators (PAMs) that target NMDARs to address neurological and psychiatric conditions.

Keywords:
CognitionGlutamate receptorIon channelN-methyl-D-aspartate receptorPositive allosteric modulatorSchizophreniaSynaptic transmission.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • N-methyl-D-aspartate receptors (NMDARs) are key ionotropic glutamate receptors crucial for synaptic plasticity and brain signaling.
  • Dysfunctional NMDAR signaling is implicated in numerous neurological and psychiatric disorders, affecting cognitive functions like learning and memory.

Purpose of the Study:

  • To provide a high-level overview of NMDAR research.
  • To discuss the various chemical classes of positive allosteric modulators (PAMs) discovered for NMDARs.
  • To highlight ongoing opportunities in NMDAR pharmacology.

Main Methods:

  • Review of existing literature on NMDARs and their modulators.
  • Analysis of different chemotypes and binding sites of NMDAR PAMs.
  • Discussion of NMDAR subtype heterogeneity and pharmacological properties.

Main Results:

  • NMDARs are complex receptors with diverse subtypes and pharmacological properties.
  • Various chemotypes of PAMs have been identified, binding to different sites on the NMDAR.
  • NMDAR hypofunction is a target for CNS drug discovery, with PAMs showing therapeutic potential.

Conclusions:

  • NMDAR research continues to yield novel mechanistic insights into receptor activation.
  • The heterogeneity of NMDARs and their modulators offers broad opportunities for drug discovery.
  • PAMs represent a promising strategy for developing treatments for NMDAR-related disorders.