ArticleEuropean journal of pharmacology2013
Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors.
Article in European journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 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
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- The role of nicotinic receptors in alcohol consumption.Pharmacological research · 2023Pooled it
- A systematic review of therapeutic ketamine use in children and adolescents with treatment-resistant mood disorders.European child & adolescent psychiatry · 2021Pooled it
- Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.British journal of clinical pharmacology · 2026Trial
- Acute Dissociation and Ketamine's Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial.The international journal of neuropsychopharmacology · 2024Trial
- Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection.British journal of anaesthesia · 2023Trial
- Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment.Clinical pharmacokinetics · 2023Trial
- The Effect of Low-Dose Esketamine on Postoperative Neurocognitive Dysfunction in Elderly Patients Undergoing General Anesthesia for Gastrointestinal Tumors: A Randomized Controlled Trial.Drug design, development and therapy · 2023Trial
- Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- Dextromethorphan and memantine after ketamine analgesia: a randomized control trial.Drug design, development and therapy · 2019Trial
- d-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study.Biochimica et biophysica acta. Proteins and proteomics · 2018Trial
- The effects of low-dose ketamine and (2R,6R)-Hydroxynorketamine on affective behaviors associated with protracted oxycodone withdrawal.Psychopharmacology · 2026Article
- Increase of the AMPA-evoked response of pyramidal neurons in the rat medial prefrontal cortex following acute administration of ketamine and S-ketamine, but not R-ketamine.The international journal of neuropsychopharmacology · 2026Article
- Esketamine Nasal Spray: Mechanism of Action, Clinical, and Translational Science.Clinical and translational science · 2026Review
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Discovery and mechanism of negative allosteric modulation of the α7 nicotinic acetylcholine receptor by nanobodies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Esketamine in depression: putative biomarkers from clinical research.European archives of psychiatry and clinical neuroscience · 2025Review
- Rapid hippocampal synaptic potentiation induced by ketamine metabolite (2R,6R)-hydroxynorketamine persistently primes synaptic plasticity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Insights for the Next Generation of Ketamine for the Treatment of Depressive Disorder.Journal of medicinal chemistry · 2025Review
- Is there a risk of esketamine misuse in clinical practice?Therapeutic advances in drug safety · 2025Review
- ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 8 institutions in 2 countries.
Funding
Abstract
The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC(50) = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤ 1 μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [(125)I]-α-bungarotoxin and [(3)H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC(50) 3.1 and 9.1 μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC(50) >100 μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [(3)H]-MK-801. The calculated K(i) values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and>100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug.
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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.