ArticleThe international journal of neuropsychopharmacology2018
Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.
Article in The international journal of neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 110 citations in OpenAlex.
- Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials.JAMA network open · 2026Trial
- Ketamine metabolite pilot study in a suicidal depression trial.Journal of psychiatric research · 2019Trial
- Investigation of Potential Therapeutic Effects of New Rapid-Acting Antidepressant Drugs (RAADs) Using Stress-Based Models of Depression.Biomolecules · 2026Review
- Ketamine enantiomers and the gut microbiota: mechanisms, clinical implications, and future directions.Molecular biology reports · 2025Review
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers.Journal of anesthesia and translational medicine · 2025Review
- Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.European archives of psychiatry and clinical neuroscience · 2025Review
- Article
- Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.Journal of medicinal chemistry · 2025Review
- ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- The role of NMDARs in the anesthetic and antidepressant effects of ketamine.CNS neuroscience & therapeutics · 2024Review
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.Frontiers in pharmacology · 2024Review
- Comments to behavioral tests for antidepressant-like actions of (2R,6R)-hydroxynorketamine by Bonaventura et al.Molecular psychiatry · 2024Article
- Effects of (2R,6R)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice.PloS one · 2024Article
- (2R,6R)-Hydroxynorketamine Treatment of Rats Exposed to Repetitive Low-Level Blast Injury.Neurotrauma reports · 2023Article
- A key role of miR-132-5p in the prefrontal cortex for persistent prophylactic actions of (R)-ketamine in mice.Translational psychiatry · 2022Article
- Review
- (2R,6R)-hydroxynorketamine rapidly potentiates optically-evoked Schaffer collateral synaptic activity.Neuropharmacology · 2022Article
- BDNF-TrkB signaling-mediated upregulation of Narp is involved in the antidepressant-like effects of (2R,6R)-hydroxynorketamine in a chronic restraint stress mouse model.BMC psychiatry · 2022Article
- Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine.Translational psychiatry · 2022Article
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor.Molecular psychiatry · 2022Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. Methods: The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. Results: A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Conclusions: Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions.
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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.