ArticleACS chemical neuroscience2013
Key binding interactions for memantine in the NMDA receptor.
Article in ACS chemical neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 54 citations in OpenAlex.
- Regulation of NMDA receptor interactions with the actin cytoskeleton in dendritic spine development.Frontiers in cellular neuroscience · 2026Review
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- Donepezil and Memantine Derivatives for Dual-Function and Prodrug Applications in Alzheimer's Disease.ACS chemical neuroscience · 2025Article
- Human serum-derived α-synuclein auto-antibodies mediate NMDA receptor-dependent degeneration of CNS neurons.Journal of neuroinflammation · 2024Article
- The Role of NMDA Receptor Subunits in the Effect of Memantine on the Brain of Healthy Animals.Bulletin of experimental biology and medicine · 2023Article
- Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer's disease.European journal of medicinal chemistry · 2022Article
- Conjugation of Aminoadamantane and γ-Carboline Pharmacophores Gives Rise to Unexpected Properties of Multifunctional Ligands.Molecules (Basel, Switzerland) · 2021Article
- Synthesis and In Vitro Evaluation of Novel Dopamine Receptor DBiomolecules · 2021Article
- Article
- Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Effect of the mGluJournal of neural transmission (Vienna, Austria : 1996) · 2021Article
- Chaperone Sigma1R and Antidepressant Effect.International journal of molecular sciences · 2020Review
- Dual action of amitriptyline on NMDA receptors: enhancement of Ca-dependent desensitization and trapping channel block.Scientific reports · 2019Article
- Heterogeneous clinical and functional features of GRIN2D-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2019Article
- Pharmacological and Electrophysiological Characterization of Novel NMDA Receptor Antagonists.ACS chemical neuroscience · 2018Article
- Memantine has no effect on KBMC research notes · 2018Article
- Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.Nature communications · 2018Article
- Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases.MedChemComm · 2017Article
- N'-3-(Trifluoromethyl)phenyl Derivatives of N-Aryl-N'-methylguanidines as Prospective PET Radioligands for the Open Channel of the N-Methyl-d-aspartate (NMDA) Receptor: Synthesis and Structure-Affinity Relationships.Journal of medicinal chemistry · 2015Article
- Binding of ArgTX-636 in the NMDA receptor ion channel.Journal of molecular biology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Memantine (Namenda) is prescribed as a treatment for moderate to severe Alzheimer's Disease. Memantine functions by blocking the NMDA receptor, but the key binding interactions between drug and receptor are not fully elucidated. To determine key binding interactions of memantine, we made side-by-side comparisons of IC(50) for memantine and amantadine, a structurally related drug, in the GluN1/GluN2B NMDA receptor. We identified hydrophobic binding pockets for the two methyl groups on memantine formed by the residues A645 and A644 on the third transmembrane helices of GluN1 and GluN2B, respectively. Moreover, we found that while adding two methyl groups to amantadine to produce memantine greatly improves affinity, adding a third methyl group to produce the symmetrical trimethylamantadine diminished affinity. Our results provide a better understanding of chemical-scale interactions between memantine and the NMDA channel, which will potentially benefit the development of new drugs for neurodegenerative diseases involving NMDA receptors.
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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.