ArticleScientific reports2018
Lack of metabolism in (R)-ketamine's antidepressant actions in a chronic social defeat stress model.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials.JAMA network open · 2026Trial
- Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia.Science advances · 2026Article
- 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
- Effects of (2R,6R)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice.PloS one · 2024Article
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.Frontiers in pharmacology · 2024Review
- Article
- Target deconvolution studies of (2R,6R)-hydroxynorketamine: an elusive search.Molecular psychiatry · 2022Article
- Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted.International journal of molecular sciences · 2022Article
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor.Molecular psychiatry · 2022Review
- Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.Cell reports · 2021Article
- Hydroxynorketamines: Pharmacology and Potential Therapeutic Applications.Pharmacological reviews · 2021Review
- The stress susceptibility factor FKBP51 controls S-ketamine-evoked release of mBDNF in the prefrontal cortex of mice.Neurobiology of stress · 2020Article
- Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression.Molecular brain · 2020Article
- Muscone reduced the hypnotic and analgesic effect of ketamine in mice.Journal of the Chinese Medical Association : JCMA · 2020Article
- Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1.Translational psychiatry · 2020Article
- Rodent ketamine depression-related research: Finding patterns in a literature of variability.Behavioural brain research · 2019Review
- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites.Translational psychiatry · 2019Review
- What role does the (2R,6R)-hydronorketamine metabolite play in the antidepressant-like and abuse-related effects of (R)-ketamine?British journal of pharmacology · 2019Article
- Rapid-acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective.Psychiatry and clinical neurosciences · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since the metabolism of (R,S)-ketamine to (2R,6R)-hydroxynorketamine (HNK) is reported to be essential for ketamine's antidepressant effects, there is an increasing debate about antidepressant effects of (2R,6R)-HNK. Using pharmacokinetic and behavioral techniques, we investigated whether intracerebroventricular (i.c.v.) infusion of (R)-ketamine or (2R,6R)-HNK show antidepressant effects in a chronic social defeat stress (CSDS) model of depression. Low levels of (2R,6R)-HNK in the brain after i.c.v. infusion of (R)-ketamine were detected, although brain levels of (2R,6R)-HNK were markedly lower than those after i.c.v. infusion of (2R,6R)-HNK. Furthermore, high levels of (2R,6R)-HNK in the blood and liver after i.c.v. infusion of (R)-ketamine or (2R,6R)-HNK were detected. A single i.c.v. infusion of (R)-ketamine showed rapid and long-lasting (7 days) antidepressant effects in a CSDS model. In contrast, i.c.v. infusion of (2R,6R)-HNK did not show any antidepressant effect in the same model, although brain concentration of (2R,6R)-HNK was higher than after i.c.v. infusion of (R)-ketamine. This study suggest that (R)-ketamine in the periphery after washout from the brain is metabolized to (2R,6R)-HNK in the liver, and subsequently, (2R,6R)-HNK enters into brain tissues. Furthermore, it is unlikely that (2R,6R)-HNK is essential for the antidepressant actions of (R)-ketamine in a CSDS model.
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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.