Mg2+Imparts NMDA Receptor Subtype Selectivity to the Alzheimer's Drug Memantine
Open accessAbstract
N-Methyl-d-aspartate receptors (NMDARs) mediate interneuronal communication and are broadly involved in nervous system physiology and pathology (Dingledine et al., 1999). Memantine, a drug that blocks the ion channel formed by NMDARs, is a widely prescribed treatment of Alzheimer's disease (Schmitt, 2005; Lipton, 2006; Parsons et al., 2007). Research on memantine's mechanism of action has focused on the NMDAR subtypes most highly expressed in adult cerebral cortex, NR1/2A and NR1/2B receptors (Cull-Candy and Leszkiewicz, 2004), and has largely ignored interactions with extracellular Mg 2+(Mg 2+o). Mg 2+o is an endogenous NMDAR channel blocker that binds near memantine's binding site (Kashiwagi et al., 2002; Chen and Lipton, 2005). We report that a physiological concentration (1 m m) of Mg 2+o decreased memantine inhibition of NR1/2A and NR1/2B receptors nearly 20-fold at a membrane voltage near rest. In contrast, memantine inhibition of the other principal NMDAR subtypes, NR1/2C and NR1/2D receptors, was decreased only ∼3-fold. As a result, therapeutic memantine concentrations should have negligible effects on NR1/2A or NR1/2B receptor activity but pronounced effects on NR1/2C and NR1/2D receptors. Quantitative modeling showed that the voltage dependence of memantine inhibition also is altered by 1 m m Mg 2+o. We report similar results with the NMDAR channel blocker ketamine, a drug used to model schizophrenia (Krystal et al., 2003). These results suggest that currently hypothesized mechanisms of memantine and ketamine action should be reconsidered and that NR1/2C and/or NR1/2D receptors play a more important role in cortical physiology and pathology than previously appreciated.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Without Mg2+, ketamine IC50 values are lower for GluN2A/B/C/D receptors (0.33, 0.31, 0.51, and 0.83 μM).
“Importantly, in the absence of Mg2+, the IC50 values of ketamine are lower for GluN2A/B/C/D (0.33, 0.31, 0.51, and 0.83 μM respectively).”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Kotermanski & Johnson, 2009
The Results report that adding 1 mM Mg²⁺ right-shifted ketamine concentration–inhibition curves for all four NR1/2 subtypes, supporting lower IC₅₀ values without Mg²⁺. The passages available from our copy do not give the four claimed values (0.33, 0.31, 0.51, and 0.83 μM), so those numbers cannot be verified. (LLM, conf=0.84)
Experimental — accuracy not yet measuredUnder physiological Mg2+, glutamate, glycine, and pH 7.2, GluN2C/D-containing NMDARs in HEK293T cells are more sensitive to ketamine block (IC50 1.18 and 2.95 μM) than GluN2A/B-containing receptors (5.35 and 5.08 μM).
“For instance, GluN2C/D-containing NMDARs expressed in HEK293T cells appear to be more susceptible to ketamine block (IC50 of 1.18 and 2.95 μM, respectively) in the presence of physiological 1 mM Mg2+, 1 mM glutamate, 100 μM glycine, and pH 7.2 relative to GluN2A/B (5.35 and 5.08 μM, respectively) containing NMDARs”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Kotermanski & Johnson, 2009
The Results and Discussion report that, in 1 mM Mg2+, ketamine preferentially inhibits NR1/2C and NR1/2D receptors over NR1/2A and NR1/2B. The Methods confirm HEK293T cells, 1 mM glutamate, 100 μM glycine, and pH 7.2. The passages available from our copy do not give the four quoted ketamine IC50 values, so those numbers cannot be verified. (LLM, conf=0.84)
Experimental — accuracy not yet measuredKotermanski and Johnson proposed that ketamine may be somewhat selective for GluN2C/D-containing NMDARs when physiological Mg2+ is present.
“These authors suggest that ketamine may have some selectivity for GluN2C/D-containing NMDARs in the presence of physiological Mg2+”
From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Kotermanski & Johnson, 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 2× · see citing works
“The clinical utility of memantine may be enhanced by its inhibition of -7 nAChRs [reported memantine IC50 ranges from 0.34 (Aracava et al., 2005) to 5 M (Maskell et al., 2003)], receptors that participate in amyloid- - induced NMDAR internalization (Snyder et al., 2005).”
InfluentialKuner, T., & Schoepfer, R. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-11-03549.1996 · Cited by 235 · see citing works
Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia†
Greene, R. (2001) · Hippocampus · doi:10.1002/hipo.1072 · Cited by 140 · see citing works
Flagged first, then by citations
Research works printed but not linked: 31
- Annetta MG Iemma D Garisto C Tafani C Proietti R 2005 Ketamine: new indications for an old drug Current Drug Targets 6 789 794 16305457
- Aracava Y Pereira EF Maelicke A Albuquerque EX 2005 Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than N-methyl-D-aspartate receptors in rat hippocampal neurons Journal of Pharmacology & Experimental Therapeutics 312 1195 1205 15522999
- Bell KF Claudio Cuello A 2006 Altered synaptic function in Alzheimer's disease Eur J Pharmacol 545 11 21 16887118
- Blanpied TA Boeckman FA Aizenman E Johnson JW 1997 Trapping channel block of NMDA-activated responses by amantadine and memantine J Neurophysiol 77 309 323 9120573
- Chen HSV Lipton SA 2005 Pharmacological implications of two distinct mechanisms of interaction of memantine with N-methyl-D-aspartate-gated channels Journal of Pharmacology and Experimental Therapeutics 314 961 971 15901795
- Cull-Candy SG Leszkiewicz DN 2004 Role of distinct NMDA receptor subtypes at central synapses Sci STKE 2004 re16 15494561
- D'Andrea MR Nagele RG 2006 Targeting the alpha 7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer's disease pyramidal neurons Curr Pharm Des 12 677 684 16472157
- David HN Ansseau M Lemaire M Abraini JH 2006 Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization Biol Psychiatry 60 49 57 16427030
- Dingledine R Borges K Bowie D Traynelis SF 1999 The glutamate receptor ion channels Pharmacol Rev 51 7 61 10049997
- Dravid SM Erreger K Yuan H Nicholson K Le P Lyuboslavsky P Almonte A Murray E Mosely C Barber J French A Balster R Murray TF Traynelis SF 2007 Subunit-specific mechanisms and proton sensitivity of NMDA receptor channel block J Physiol 581 107 128 17303642 PMC2075223
- Homayoun H Moghaddam B 2007 NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons J Neurosci 27 11496 11500 17959792 PMC2954603
- Johnson JW Kotermanski SE 2006 Mechanism of action of memantine Curr Opin Pharmacol 6 61 67 16368266
- Kashiwagi K Masuko T Nguyen CD Kuno T Tanaka I Igarashi K Williams K 2002 Channel blockers acting at N-methyl-D-aspartate receptors: differential effects of mutations in the vestibule and ion channel pore Mol Pharmacol 61 533 545 11854433
- Krystal JH D'Souza DC Mathalon D Perry E Belger A Hoffman R 2003 NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development Psychopharmacology (Berl) 169 215 233 12955285
- Kutsuwada T Kashiwabuchi N Mori H Sakimura K Kushiya E Araki K Meguro H Masaki H Kumanishi T Arakawa M 1992 Molecular diversity of the NMDA receptor channel Nature 358 36 41 1377365
- Le Meur K Galante M Angulo MC Audinat E 2007 Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus J Physiol 580 373 383 17185337 PMC2075557
- Lerma J Zukin RS Bennett MV 1991 Interaction of Mg2+ and phencyclidine in use-dependent block of NMDA channels Neurosci Lett 123 187 191 1709267
- Lipton SA 2006 Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond Nat Rev Drug Discov 5 160 170 16424917
- Lisman JE Coyle JT Green RW Javitt DC Benes FM Heckers S Grace AA 2008 Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia Trends Neurosci 31 234 242 18395805 PMC2680493
- Liu HT Hollmann MW Liu WH Hoenemann CW Durieux ME 2001 Modulation of NMDA receptor function by ketamine and magnesium: Part I Anesthesia & Analgesia 92 1173 1181 11323343
- MacDonald JF Bartlett MC Mody I Pahapill P Reynolds JN Salter MW Schneiderman JH Pennefather PS 1991 Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones J Physiol (Lond) 432 483 508 1832184 PMC1181337
- Maskell PD Speder P Newberry NR Bermudez I 2003 Inhibition of human alpha 7 nicotinic acetylcholine receptors by open channel blockers of N-methyl-D-aspartate receptors British Journal of Pharmacology 140 1313 1319 14645141 PMC1574144
- Moghaddam B Jackson ME 2003 Glutamatergic animal models of schizophrenia Ann N Y Acad Sci 1003 131 137 14684441
- Monyer H Burnashev N Laurie DJ Sakmann B Seeburg PH 1994 Developmental and regional expression in the rat brain and functional properties of four NMDA receptors Neuron 12 529 540 7512349
- Oliver D Ludwig J Reisinger E Zoellner W Ruppersberg JP Fakler B 2001 Memantine inhibits efferent cholinergic transmission in the cochlea by blocking nicotinic acetylcholine receptors of outer hair cells Molecular Pharmacology 60 183 189 11408613
- Parsons CG Stoffler A Danysz W 2007 Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse Neuropharmacology 53 699 723 17904591
- Qian A Johnson JW 2006 Permeant ion effects on external Mg2+ block of NR1/2D NMDA receptors J Neurosci 26 10899 10910 17050728 PMC6674757
- Rogawski MA Wenk GL 2003 The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease CNS Drug Reviews 9 275 308 14530799 PMC6741669
- Schmitt HP 2005 On the paradox of ion channel blockade and its benefits in the treatment of Alzheimer disease Med Hypotheses 65 259 265 15922097
- Sobolevsky AI Koshelev SG Khodorov BI 1998 Interaction of memantine and amantadine with agonist-unbound NMDA- receptor channels in acutely isolated rat hippocampal neurons J Physiol 512 47 60 9729616 PMC2231181
- Yamakura T Mori H Masaki H Shimoji K Mishina M 1993 Different sensitivities of NMDA receptor channel subtypes to non- competitive antagonists Neuroreport 4 687 690 8347808
Cited by
Sorted by citations
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
Paoletti, P., Bellone, C., & Zhou, Q. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3504 · Cited by 2,523 · see citing works
Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders
Hardingham, G. E., & Bading, H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2911 · Cited by 1,644 · see citing works
Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms
Zanos, P., Moaddel, R., Morris, P. J., Riggs, L. M., Highland, J. N., Georgiou, P., Pereira, E. F. R., Albuquerque, E. X., Thomas, C. J., Zarate, C. A., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015198 · Cited by 1,260 · see citing works
Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127 · see citing works
The role of default network deactivation in cognition and disease
Anticevic, A., Cole, M. W., Murray, J. D., Corlett, P. R., Wang, X.-J., & Krystal, J. H. (2012) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2012.10.008 · Cited by 978 · see citing works
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression.
Newport, D. J., Carpenter, L. L., McDonald, W. M., Potash, J. B., Tohen, M., Nemeroff, C. B., & The APA Council of Research Task Force on Novel Biomarkers and Treatments (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15040465 · Cited by 598 · see citing works
GABAergic interneuron origin of schizophrenia pathophysiology
Nakazawa, K., Zsiros, V., Jiang, Z., Nakao, K., Kolata, S., Zhang, S., & Belforte, J. E. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.022 · Cited by 498 · see citing works
Dysfunction of NMDA receptors in Alzheimer’s disease
Zhang, Y., Li, P., Feng, J., & Wu, M. (2016) · Neurological Sciences · doi:10.1007/s10072-016-2546-5 · Cited by 282 · see citing works
“Memantine, a drug that blocks NMDARs, is widely used in treating AD patients, although its mechanism is still in debate [20].”
BackgroundAcute suppression of spontaneous neurotransmission drives synaptic potentiation
Nosyreva, E., Szabla, K., Autry, A. E., Ryazanov, A. G., Monteggia, L. M., & Kavalali, E. T. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4998-12.2013 · Cited by 283 · see citing works
“However, it is important to note that the inhibition of NMDA mEPSCs by ketamine or MK-801 is expected to be less effective in the presence of physiological concentrations of Mg2 (Kotermanski and Johnson, 2009).”
BackgroundAnticevic, A., Gancsos, M., Murray, J. D., Repovs, G., Driesen, N. R., Ennis, D. J., Niciu, M. J., Morgan, P. T., Surti, T. S., Bloch, M. H., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208494109 · Cited by 243 · see citing works
Murray, J. D., Anticevic, A., Gancsos, M., Ichinose, M., Corlett, P. R., Krystal, J. H., & Wang, X.-J. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhs370 · Cited by 255 · see citing works
Influence of GluN2 subunit identity on NMDA receptor function
Wyllie, D. J. A., Livesey, M. R., & Hardingham, G. E. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.01.016 · Cited by 260 · see citing works
Ketamine: NMDA Receptors and Beyond
Zorumski, C. F., Izumi, Y., & Mennerick, S. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1547-16.2016 · Cited by 254 · see citing works
Gideons, E. S., Kavalali, E. T., & Monteggia, L. M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323920111 · Cited by 232 · see citing works
Miller, O. H., Moran, J. T., & Hall, B. J. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.028 · Cited by 200 · see citing works
Pham, T. H., & Gardier, A. M. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.017 · Cited by 186 · see citing works
Mechanisms of ketamine and its metabolites as antidepressants
Hess, E. M., Riggs, L. M., Michaelides, M., & Gould, T. D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114892 · Cited by 169 · see citing works
Lumsden, E. W., Troppoli, T. A., Myers, S. J., Zanos, P., Aracava, Y., Kehr, J., Lovett, J., Kim, S., Wang, F.-H., Schmidt, S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1816071116 · Cited by 158 · see citing works
Alzheimer's disease amyloid β-protein and synaptic function
Ondrejcak, T., Klyubin, I., Hu, N.-W., Barry, A. E., Cullen, W. K., & Rowan, M. J. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8091-0 · Cited by 146 · see citing works
Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models
O'Donnell, P. (2011) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr028 · Cited by 145 · see citing works
Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants
Gould, T. D., Zarate, C. A., & Thompson, S. M. (2019) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010617-052811 · Cited by 133 · see citing works
“One study reports that ketamine exerts greater inhibition of GluN2C- and GluN2D-containing NMDARs than of GluN2A- and GluN2B-containing subunits (61).”
BackgroundStys, P. K., You, H., & Zamponi, G. W. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.225276 · Cited by 115 · see citing works
Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia
Nakazawa, K., Jeevakumar, V., & Nakao, K. (2017) · npj Schizophrenia · doi:10.1038/s41537-016-0003-3 · Cited by 110 · see citing works
Zhang, K., Xu, T., Yuan, Z., Wei, Z., Yamaki, V. N., Huang, M., Huganir, R. L., & Cai, X. (2016) · Science Signaling · doi:10.1126/scisignal.aai7884 · Cited by 98 · see citing works
Exposure of metal toxicity in Alzheimer’s disease: An extensive review
Islam, F., Shohag, S., Akhter, S., Islam, M. R., Sultana, S., Mitra, S., Chandran, D., Khandaker, M. U., Ashraf, G. M., Idris, A. M., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.903099 · Cited by 83 · see citing works
Metaplastic Effects of Subanesthetic Ketamine on CA1 Hippocampal Function
Izumi, Y., & Zorumski, C. F. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.08.002 · Cited by 63 · see citing works
Zorumski, C. F., Nagele, P., Mennerick, S., & Conway, C. R. (2015) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2015.00172 · Cited by 57 · see citing works
Differential regulation of GluA1 expression by ketamine and memantine
Zhang, K., Yamaki, V. N., Wei, Z., Zheng, Y., & Cai, X. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.09.002 · Cited by 51 · see citing works
Targeting metaplasticity mechanisms to promote sustained antidepressant actions
Brown, K. A., & Gould, T. D. (2024) · Molecular Psychiatry · doi:10.1038/s41380-023-02397-1 · Cited by 49 · see citing works
Riebe, I., Seth, H., Culley, G., Dósa, Z., Radi, S., Strand, K., Fröjd, V., & Hanse, E. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13128 · Cited by 40 · see citing works
Ingram, R., Kang, H., Lightman, S., Jane, D. E., Bortolotto, Z. A., Collingridge, G. L., Lodge, D., & Volianskis, A. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.06.008 · Cited by 36 · see citing works
Bettini, E., Stahl, S. M., De Martin, S., Mattarei, A., Sgrignani, J., Carignani, C., Nola, S., Locatelli, P., Pappagallo, M., Inturrisi, C. E., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15080997 · Cited by 31 · see citing works
De Martin, S., Gabbia, D., Folli, F., Bifari, F., Fiorina, P., Ferri, N., Stahl, S., Inturrisi, C. E., Pappagallo, M., Traversa, S., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.671859 · Cited by 28 · see citing works
Turcu, A. L., Companys-Alemany, J., Phillips, M. B., Patel, D. S., Griñán-Ferré, C., Loza, M. I., Brea, J. M., Pérez, B., Soto, D., Sureda, F. X., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114354 · Cited by 27 · see citing works
- Authors
- Kotermanski, S. E., & Johnson, J. W.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Johnson, Jon W.
- ORCID
- Johnson, Jon W.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-03-04
- Volume
- 29
- Issue
- 9
- Pages
- 2774-2779
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2679254
- OpenAlex
- W1997962734
- Cited by
- 271
- References
- 3
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 15 · 2023: 11 · 2022: 18 · 2021: 12 · 2020: 15 · 2019: 14 · 2018: 12 · 2017: 16 · 2016: 18 · 2015: 23 · 2014: 13 · 2013: 23 · 2012: 13
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- University of Pittsburgh
- National Institutes of Health
- National Institute of Mental Health (R01MH045817)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- memantine, magnesium, NMDA receptor subtypes, Alzheimer's disease, ketamine, receptor subtype selectivity, ion channel blockade, cortical physiology
- MeSH terms
- Alzheimer Disease, Cells, Cultured, Data Interpretation, Statistical, Electrophysiology, Humans, Ketamine, Magnesium, Memantine, Transfection, Receptors, N-Methyl-D-Aspartate, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
