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Related Experiment Video

Updated: May 14, 2026

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
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Published on: July 10, 2018

Key binding interactions for memantine in the NMDA receptor.

Walrati Limapichat1, Wesley Y Yu, Emma Branigan

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

ACS Chemical Neuroscience
|February 21, 2013
PubMed
Summary

Memantine, used for Alzheimer's disease, binds to NMDA receptors. Researchers identified specific binding interactions, revealing how memantine's structure affects its effectiveness against neurodegenerative diseases.

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Published on: August 16, 2018

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Memantine is a key treatment for moderate to severe Alzheimer's Disease.
  • Its mechanism involves blocking the N-methyl-D-aspartate (NMDA) receptor.
  • The precise binding interactions of memantine within the NMDA receptor remain incompletely understood.

Purpose of the Study:

  • To elucidate the key binding interactions between memantine and the NMDA receptor.
  • To compare the binding affinities of memantine and amantadine.
  • To understand how structural modifications affect drug-receptor interactions.

Main Methods:

  • Side-by-side comparison of IC(50) values for memantine and amantadine.
  • Utilized the GluN1/GluN2B NMDA receptor subtype for experiments.
  • Identified specific amino acid residues involved in drug binding.

Main Results:

  • Identified hydrophobic binding pockets for memantine's methyl groups involving residues A645 (GluN1) and A644 (GluN2B).
  • Adding two methyl groups (amantadine to memantine) significantly enhanced binding affinity.
  • Adding a third methyl group (trimethylamantadine) reduced binding affinity.

Conclusions:

  • Detailed understanding of memantine's chemical-scale interactions with the NMDA channel.
  • Provides insights into structure-activity relationships for NMDA receptor ligands.
  • Potential to guide the development of novel therapeutics for neurodegenerative diseases targeting NMDA receptors.