Related Experiment Video
Updated: Sep 17, 2025
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
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Memantine inhibits calcium-permeable AMPA receptors
Elisa Carrillo1, Alejandra Montaño Romero2,3, Cuauhtemoc U Gonzalez4,5
1Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX, USA. elisa.carrilloflores@uth.tmc.edu.
Nature Communications
|July 2, 2025
Summary
Memantine, an FDA-approved drug, inhibits calcium-permeable AMPA receptors (CP-AMPARs), not just NMDA receptors. This discovery offers new therapeutic strategies for neurological disorders by targeting CP-AMPARs.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- NMDA receptors (NMDARs) regulate calcium influx, crucial for brain function.
- Aberrant calcium influx via AMPA receptors (AMPARs) is implicated in neurological diseases.
- Memantine is an FDA-approved drug targeting NMDARs.
Purpose of the Study:
- To investigate if memantine inhibits calcium-permeable AMPARs (CP-AMPARs).
- To elucidate the mechanism of memantine's action on CP-AMPARs.
- To explore memantine's effect on CP-AMPARs in neurodevelopmental disorders.
Main Methods:
- Electrophysiology to study memantine's inhibition of CP-AMPARs.
- Cryo-electron microscopy to determine the structural basis of inhibition.
- Functional assays on mutated AMPARs associated with neurodevelopmental disorders.
Main Results:
- Memantine effectively inhibits CP-AMPARs, dependent on calcium permeability and TARP co-assembly.
- Cryo-EM reveals a unique binding and blocking mechanism distinct from NMDAR inhibition.
- Memantine demonstrated inhibitory effects on a gain-of-function AMPAR mutation linked to neurodevelopmental disorders.
Conclusions:
- Memantine possesses inhibitory activity against CP-AMPARs.
- The findings reveal a novel mechanism of action for memantine.
- This study highlights CP-AMPARs as potential therapeutic targets for neurological conditions.
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