ArticleNeurobiology of disease2016
Effects of memantine on the excitation-inhibition balance in prefrontal cortex.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809).Translational psychiatry · 2022Trial
- Memantine Effects on Electroencephalographic Measures of Putative Excitatory/Inhibitory Balance in Schizophrenia.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Trial
- Single-Dose Memantine Improves Cortical Oscillatory Response Dynamics in Patients with Schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Selective mGluBiological psychiatry global open science · 2026Article
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- State-specific inhibition of NMDA receptors by memantine provides insight into NMDAR channel blocker tolerability.Science advances · 2026Article
- Article
- Increased NMDAR activity and GluN2A-NMDAR silent synapse expansion induced by chronic benzodiazepine treatment.Neuropharmacology · 2025Article
- Do cognitive and neurophysiological effects of acute memantine "challenge" predict its clinical benefits in Alzheimer's Disease?Psychiatry research · 2025Article
- Synaptic basis of rapid antidepressant action.European archives of psychiatry and clinical neuroscience · 2025Review
- MeCP2 prevents against sustained ketamine-induced synaptic depression at inhibitory synapses.iScience · 2025Article
- Chronic benzodiazepine treatment triggers gephyrin scaffold destabilization and GABAFrontiers in cellular neuroscience · 2025Article
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Sex-specific effects of subchronic NMDA receptor antagonist MK-801 treatment on hippocampal gamma oscillations.Frontiers in neuroscience · 2024Article
- Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.Neuropharmacology · 2023Article
- Rapid homeostatic plasticity and neuropsychiatric therapeutics.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Pathway-specific contribution of parvalbumin interneuron NMDARs to synaptic currents and thalamocortical feedforward inhibition.Molecular psychiatry · 2022Article
- mGluNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- The neurophysiological effect of NMDA-R antagonism of frontotemporal lobar degeneration is conditional on individual GABA concentration.Translational psychiatry · 2022Article
- Sustained treatment with an α5 GABA A receptor negative allosteric modulator delays excitatory circuit development while maintaining GABAergic neurotransmission.Neuropharmacology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Memantine is one of the few drugs currently approved for treatment of Alzheimer's disease (AD). The clinical effects of memantine are thought to be associated with inhibition of NMDA receptors (NMDARs). Surprisingly, other open-channel NMDAR blockers have unacceptable side effects that prevent their consideration for AD treatment. One of the mechanisms proposed to explain the therapeutic benefits of memantine involves preferential decrease of excitatory drive to inhibitory neurons in the cortical circuitry and consequent changes in balance between excitation and inhibition (E/I). In this study we addressed effects of memantine on E/I balance in the prefrontal cortex (PFC). We found that a moderate concentration of memantine shifted E/I balance away from inhibition in the PFC circuitry. Indeed, memantine decreased the frequency and amplitude of spontaneous inhibitory postsynaptic currents in pyramidal neurons while leaving spontaneous excitatory postsynaptic currents unaffected. These circuitry effects of memantine were occluded by the competitive NMDAR inhibitor AP-5, and thus are associated with NMDAR inhibition. We also found that memantine decreased feed-forward disynaptic inhibitory input to pyramidal neurons, which is thought to be mediated by parvalbumin (PV)-positive interneurons. Accordingly, memantine caused a greater decrease of the amplitude of NMDAR-mediated synaptic responses in PV-positive interneurons than in pyramidal neurons. Finally, memantine reduced firing activity in PV-positive interneurons while increasing firing in pyramidal neurons. This study elucidates a novel mechanism of action of memantine associated with shifting of the E/I balance away from inhibition in neocortical circuitry, and provides important insights for AD drug development.
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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.