ReviewPharmacological reviews2021
Hydroxynorketamines: Pharmacology and Potential Therapeutic Applications.
Registry-linked trialOpen access · bronzeAbstract readReview
In one paragraph
Review in Pharmacological reviews, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05864053 (), which is not on this map. Cited by 51 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 3 pooled it
11.6field-weighted citation impact, top 1% of its field
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.
NCT05864053 phase1 / phase2recruitingnot on this mapstarted 2024, after this paper: background citation
(2R,6R)-Hydroxynorketamine a Novel Therapeutic Analgesic for the Treatment of Neuropathic Pain: A Randomized Double Blind Cross-Over Trial.
Who cites it
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Ketamine treatment for refractory anxiety: A systematic review.British journal of clinical pharmacology · 2022Pooled it
- Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis.Molecular psychiatry · 2022Pooled it
- Pooled it
- Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.British journal of clinical pharmacology · 2026Trial
- Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study.Journal of psychopharmacology (Oxford, England) · 2025Trial
- A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers.Clinical pharmacology and therapeutics · 2024Trial
- Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial.Nature medicine · 2024Trial
- Sex-dependent metabolism of ketamine and (Journal of psychopharmacology (Oxford, England) · 2022Trial
- Ketamine persists within neuronal compartments long after systemic clearance.Research square · 2026Article
- Somatostatin-expressing neurons in the zona incerta regulate chronic stress response and modulate depression-like behaviors.Molecular psychiatry · 2026Article
- Prefrontal contribution to passive coping behaviour in chronic stress and treatment by fast-acting antidepressant.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The nonhallucinogenic ketamine metabolite (2R,6R)-hydroxynorketamine is a novel analgesic in animal models of pain.Frontiers in pain research (Lausanne, Switzerland) · 2026Review
- Inhibition of SERT and NMDAR synergistically confers rapid antidepressant effects of ketamine.National science review · 2025Article
- Article
- Bioactive ketamine metabolite exerts in vivo neuroplastogenic effects to improve hippocampal function in a treatment-resistant depression model.Cell reports · 2025Article
- Article
- Prophylactic (R,S)-Ketamine and (2S,6S)-Hydroxynorketamine Decrease Fear Expression by Differentially Modulating Fear Neural Ensembles.Biological psychiatry · 2025Article
- 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
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.Biomedicines · 2024Review
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 6 institutions in 1 country.
Jaclyn N HighlandDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Panos ZanosDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Lace M RiggsDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Polymnia GeorgiouDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Sarah M ClarkDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Patrick J MorrisDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Ruin MoaddelDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Craig J ThomasDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Carlos A ZarateDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Edna F R PereiraDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.).
Todd D GouldDepartments of Psychiatry (J.N.H., P.Z., L.M.R., P.G., S.M.C., T.D.G.), Pharmacology (P.Z., T.D.G.), Physiology (P.Z.), Anatomy and Neurobiology (T.D.G), Epidemiology and Public Health, Division of Translational Toxicology (E.F.R.P.), Programs in Toxicology (J.N.H.) and Neuroscience (L.M.R.), and Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland (T.D.G.); Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Intramural Research Program, National Institutes of Health, Rockville, Maryland (P.J.M., C.J.T.); Biomedical Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland (R.M.); Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (C.A.Z.) gouldlab@me.com.
National Institute on Aging · USInstitute on Aging · USNational Center for Advancing Translational Sciences · USNational Institute of Mental Health · USNational Institutes of Health · USUniversity of Maryland, Baltimore · US
Funding
Glutamatergic Modulators for Rapid & Sustained Antidepressant EffectZIAMH002857 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2009 to 2025
$55.0MTarget validation of novel therapeutic agents in mood disordersZIAMH002927 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI ZARATE, CARLOS · 2010 to 2025
$37.1MDevelopment of (R,R)-dehydronorketamine for treatment resistant depressionZIATR000042 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2015 to 2022
$18.5MEXPAND PARTICIPATION BY MINORITIES IN BIOMEDICAL SCIENCER25GM055036 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SUMMERS, MICHAEL FINLEY · 1996 to 2021
$16.9MTherapeutic Efficacy of Ketamine Metabolites for Depression TreatmentR01MH107615 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI GOULD, TODD D · 2016 to 2025
$7.2MTRAINING PROGRAM IN INTEGRATIVE MEMBRANE BIOLOGYT32GM008181 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI RIZZO, MEGAN A, TRUDEAU, MATTHEW C · 1987 to 2022
$4.9MTraining Program in NeuroscienceT32NS063391 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI Jessica Aurora Mong · 2008 to 2026
$4.0MMechanisms of sustained anti-neuroinflammatory actions of (2R, 6R)-hydroxynorketamine (HNK)R21AI145211 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI CLARK, SARAH MICHELLE, GOULD, TODD D · 2020 to 2021
$425kSynaptic mechanisms underlying the rapid antidepressant properties of the (2R,6R)-hydroxynorketamine metaboliteF31MH123066 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI RIGGS, LACE MARIE · 2020 to 2021
$55kHydroxynorketamine for the Treatment of PTSD and AnhedoniaI01BX004062 · VA · BALTIMORE VA MEDICAL CENTER · PI GOULD, TODD D · 2019 to 2023
–Targeting the inflammatory response to treat post-traumatic anxiety and depression.I01BX003631 · VA · BALTIMORE VA MEDICAL CENTER · PI GOULD, TODD D · 2017 to 2021
–BLRD VA I01 BX003631BLRD VA I01 BX004062NIAID NIH HHS R21 AI145211NIGMS NIH HHS R25 GM055036NIGMS NIH HHS T32 GM008181NIMH NIH HHS F31 MH123066NIMH NIH HHS R01 MH107615NINDS NIH HHS T32 NS063391
Abstract
Hydroxynorketamines (HNKs) are formed in vivo after (
Indexed as
AnestheticsKetamineAntidepressive AgentsDepressionHumansSynaptic TransmissionAnestheticsAntidepressive AgentsKetamine
Identifiers
What Socratic holds
Textmetadata
Read underepoch 390
Registered trials
NCT05864053ClinicalTrials.gov
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 Socratic graph.