ArticlePloS one2014
Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Dextromethorphan Beyond the Cough: Exploring Its Psychedelic Potential: A Systematic Review.CNS drugs · 2026Pooled it
- Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials.CNS drugs · 2023Pooled it
- Dextromethorphan and memantine after ketamine analgesia: a randomized control trial.Drug design, development and therapy · 2019Trial
- NMDA Receptor Subunit NMR-2 Regulates Pathogen-Induced Immune Responses via the Nervous System inbioRxiv : the preprint server for biology · 2026Article
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Evaluation of the therapeutic efficacy of the dextromethorphan-bupropion combination and its mediating pathways in a mouse model of major depressive disorder.Frontiers in pharmacology · 2026Article
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Article
- Advancing depression treatment: the role of sigma receptor ligands.Frontiers in neuroscience · 2025Review
- ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- SAL0114: a novel deuterated dextromethorphan-bupropion combination with improved antidepressant efficacy and safety profile.Frontiers in pharmacology · 2024Article
- Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Review
- Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder.Translational psychiatry · 2023Review
- Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome.Nature cardiovascular research · 2022Article
- Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice.Alcoholism, clinical and experimental research · 2021Article
- N-Substituted-3-alkoxy-derivatives of dextromethorphan are functional NMDA receptor antagonists in vivo: Evidence from an NMDA-induced seizure model in rats.Pharmacology, biochemistry, and behavior · 2021Article
- Insights into the biased activity of dextromethorphan and haloperidol towards SARS-CoV-2 NSP6: in silico binding mechanistic analysis.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Chaperone Sigma1R and Antidepressant Effect.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047) were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP) 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3)H](+)-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.
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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.