ReviewCurrent neuropharmacology2017
Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder.
Review in Current neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06167590 (Integrins and Protocadherins in Glutamatergic Circuits), which is not on this map. Cited by 49 papers, 2 of them syntheses that pooled 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.
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.
Integrins and Protocadherins in Glutamatergic Circuits: Identification of Common Signaling Pathways and Molecular Targets in Anxiety and Major Depressive Disorders (GAPsy)
Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Systems Approach to Identify Common Genes and Pathways Associated with Response to Selective Serotonin Reuptake Inhibitors and Major Depression Risk.International journal of molecular sciences · 2019Pooled it
- 7TNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- A Randomized, Double-Blind, Placebo-Controlled, Sequential Parallel Comparison Design Trial of Adjunctive Riluzole for Treatment-Resistant Major Depressive Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Exploring New Frontiers in Pharmacological Treatment of Depression: A Review on Recent Advances.Current medicinal chemistry · 2026Review
- The Complex Role of Serotonin-Dopamine-Glutamate Receptors in Major Depression.Advances in experimental medicine and biology · 2026Review
- Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- NMDA Receptors: Distribution, Role, and Insights into Neuropsychiatric Disorders.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Psychopharmacological Approaches for Neural Plasticity and Neurogenesis in Major Depressive Disorders.Advances in experimental medicine and biology · 2024Review
- Ketamine study: Protocol for naturalistic prospective multicenter study on subcutaneous ketamine infusion in depressed patients with active suicidal ideation.Frontiers in psychiatry · 2023Article
- Traxoprodil Produces Antidepressant-Like Behaviors in Chronic Unpredictable Mild Stress Mice through BDNF/ERK/CREB and AKT/FOXO/Bim Signaling Pathway.Oxidative medicine and cellular longevity · 2023Article
- Downregulation of surface AMPA receptor expression in the striatum following prolonged social isolation, a role of mGlu5 receptors.IBRO neuroscience reports · 2022Article
- Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research.Translational psychiatry · 2022Review
- Willardiine and Its Synthetic Analogues: Biological Aspects and Implications in Peptide Chemistry of This Nucleobase Amino Acid.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Postsynaptic Proteins at Excitatory Synapses in the Brain-Relationship with Depressive Disorders.International journal of molecular sciences · 2022Review
- Novel drug developmental strategies for treatment-resistant depression.British journal of pharmacology · 2022Review
- Roles of non-receptor tyrosine kinases in pathogenesis and treatment of depression.Journal of integrative neuroscience · 2022Review
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Major depressive disorder: Validated treatments and future challenges.World journal of clinical cases · 2021Review
- Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule.World journal of psychiatry · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Current pharmacotherapies for major depressive disorder (MDD) have a distinct lag of onset that can prolong distress and impairment for patients, and realworld effectiveness trials further suggest that antidepressant efficacy is limited in many patients. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms, e.g., receptor/reuptake agonists or antagonists with varying affinities for serotonin, norepinephrine, or dopamine. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, as well as in the development of novel therapeutics for this disorder. Since the rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000, other NMDA receptor antagonists have been studied in MDD. These have been associated with relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics with increased potential in clinical practice (for instance, oral administration, decreased dissociative and/or psychotomimetic effects, and reduced abuse/diversion liability). This article reviews the clinical evidence supporting the use of glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (NR2B)-specific NMDA receptor antagonists (CP- 101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (D-cycloserine, GLYX- 13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). Several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy, but that have yet to be studied clinically, are also briefly discussed; these include α-amino-3-hydroxyl-5-methyl-4- isoxazoleproprionic acid (AMPA) agonists, mGluR2/3 negative allosteric modulators, and mGluR7 agonists.
Indexed as
Identifiers
What OpenQuestion holds
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.