Evidence map›Paper›PMID 39770460›Full record

ReviewPharmaceuticals (Basel, Switzerland)2024

N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.

Stefano Comai, Sara De Martin, Andrea Mattarei, Clotilde Guidetti, Marco Pappagallo, Franco Folli, Andrea Alimonti, Paolo L Manfredi

Abstract readReview
In one paragraph

Review in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. [Prefrontal dysfunction and mismatch negativity in adolescent depression: A multimodal fNIRS-ERP study].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2025
    Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Stefano ComaiDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35121 Padua, Italy.ORCID 0000-0002-5686-7194
Sara De MartinDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35121 Padua, Italy.ORCID 0000-0001-6398-8237
Andrea MattareiDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35121 Padua, Italy.ORCID 0000-0002-2023-0749
Clotilde GuidettiChild Neuropsychiatry Unit, Department of Neuroscience, IRCCS Bambino Gesù Pediatric Hospital, 00165 Rome, Italy.
Marco PappagalloRelmada Therapeutics, Inc., Coral Gables, FL 33134, USA.
Franco FolliDepartment of Health Sciences, University of Milan, 20141 Milan, Italy.ORCID 0000-0001-9824-5222
Andrea AlimontiThe Institute of Oncology Research, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
Paolo L ManfrediRelmada Therapeutics, Inc., Coral Gables, FL 33134, USA.

Funding

MGGM Therapeutics and Relmada Therapeutics not applicable
6 · The paper itself

Abstract

Uncompetitive NMDAR (N-methyl-D-aspartate receptor) antagonists restore impaired neural plasticity, reverse depressive-like behavior in animal models, and relieve major depressive disorder (MDD) in humans. This review integrates recent findings from in silico, in vitro, in vivo, and human studies of uncompetitive NMDAR antagonists into the extensive body of knowledge on NMDARs and neural plasticity. Uncompetitive NMDAR antagonists are activity-dependent channel blockers that preferentially target hyperactive GluN2D subtypes because these subtypes are most sensitive to activation by low concentrations of extracellular glutamate and are more likely activated by certain pathological agonists and allosteric modulators. Hyperactivity of GluN2D subtypes in specific neural circuits may underlie the pathophysiology of MDD. We hypothesize that neural plasticity is epigenetically regulated by precise Ca

Indexed as

AMPACa2+endorphinsglutamatemajor depressive disorderMg2+neural plasticityNMDA

Identifiers

PMID39770460
PMCPMC11728621

What OpenQuestion holds

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Registered trials

None linked

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.