ArticleNature communications2025
Memantine inhibits calcium-permeable AMPA receptors.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Pre-activation and gating pathway of AMPA receptors revealed by full and partial agonists.Nature structural & molecular biology · 2026Article
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- From Atoms to Neuronal Spikes: A Multiscale Simulation Framework.Journal of chemical theory and computation · 2026Review
- From Atoms to Neuronal Spikes: A Multi-Scale Simulation Framework.bioRxiv : the preprint server for biology · 2025Article
- Structure of transmembrane AMPA receptor regulatory protein subunit γ2.Nature communications · 2025Article
- EAR-20 peptide, a novel NMDA receptor positive allosteric modulator.Frontiers in pharmacology · 2025Article
- Temperature Sensitive Glutamate Gating of AMPA-subtype iGluRs.bioRxiv : the preprint server for biology · 2024Article
- Heterogeneous responses to memantine in Alzheimer's disease: A precision medicine approach using iPSC models.Alzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
7 authors.
Funding
Abstract
Memantine is an US Food and Drug Administration (FDA) approved drug that is thought to selectively inhibit NMDA-subtype of ionotropic glutamate receptors (NMDARs). NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine blocks CP-AMPAR ion channels in a unique mechanism of action from NMDARs. Furthermore, we demonstrate that memantine inhibits a gain of function AMPAR mutation found in a patient with a neurodevelopmental disorder. Our findings unlock potential exploitation of this site to design more specific drugs targeting CP-AMPARs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.