Hydroxynorketamines: Pharmacology and Potential Therapeutic Applications

Antidepressant drugs act by directly binding to TRKB neurotrophin receptors

(2021) Plinio C. Casarotto et al.   CELL

Proteomic Study Reveals the Involvement of Energy Metabolism in the Fast Antidepressant Effect of (2R, 6R)‐Hydroxy Norketamine

(2020) Shafiq Ur Rahman et al.   Proteomics Clinical Applications

Sexually Dimorphic Behavioral Profile in a Transgenic Model Enabling Targeted Recombination in Active Neurons in Response to Ketamine and (2R,6R)-Hydroxynorketamine Administration

(2020) David P. Herzog et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Ketamine increases vmPFC activity: Effects of (R)- and (S)-stereoisomers and (2R,6R)-hydroxynorketamine metabolite

(2020) Brendan D. Hare et al.   NEUROPHARMACOLOGY

(2R,6R)-Hydroxynorketamine (HNK) plasma level predicts poor antidepressant response: is this the end of the HNK pipeline?

(2020) Chadi G. Abdallah   NEUROPSYCHOPHARMACOLOGY

Ketamine metabolites, clinical response, and gamma power in a randomized, placebo-controlled, crossover trial for treatment-resistant major depression

(2020) Cristan A. Farmer et al.   NEUROPSYCHOPHARMACOLOGY

Sex-specific neurobiological actions of prophylactic (R,S)-ketamine, (2R,6R)-hydroxynorketamine, and (2S,6S)-hydroxynorketamine

(2020) Briana K. Chen et al.   NEUROPSYCHOPHARMACOLOGY

(S)-norketamine and (2S,6S)-hydroxynorketamine exert potent antidepressant-like effects in a chronic corticosterone-induced mouse model of depression

(2020) Rei Yokoyama et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

The Ventrolateral Periaqueductal Gray Contributes to Depressive-Like Behaviors in Recovery of Inflammatory Bowel Disease Rat Model

(2020) Chih-Yuan Ko et al.   Frontiers in Neuroscience

Hydroxynorketamine Blocks N-Methyl-d-Aspartate Receptor Currents by Binding to Closed Receptors

(2020) Jamie A. Abbott et al.   MOLECULAR PHARMACOLOGY

Targeting Homeostatic Synaptic Plasticity for Treatment of Mood Disorders

(2020) Ege T. Kavalali et al.   NEURON

Brain-derived neurotrophic factor in the ventrolateral periaqueductal gray contributes to (2R,6R)-hydroxynorketamine-mediated actions

(2020) Dylan Chou   NEUROPHARMACOLOGY

Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression

(2020) Lily R. Aleksandrova et al.   Molecular Brain

Targeted mass spectrometry of ketamine and its metabolites cis-6-hydroxynorketamine and norketamine in human blood serum

(2020) Lisa Kurzweil et al.   JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES

Ketamine metabolite (2R,6R)-hydroxynorketamine reverses behavioral despair produced by adolescent trauma

(2020) Greg I. Elmer et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Separation of anaesthetic ketamine and its derivates in PAMAPTAC coated capillaries with tuneable counter-current electroosmotic flow

(2020) Petr Tůma et al.   TALANTA

Antidepressant actions of ketamine engage cell-specific translation via eIF4E

(2020) Argel Aguilar-Valles et al.   NATURE

Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions

(2020) Lauren Wegman-Points et al.   Frontiers in Pharmacology

Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain

(2019) Jeffrey S Kroin et al.   REGIONAL ANESTHESIA AND PAIN MEDICINE

(2R,6R)-hydroxynorketamine exerts mGlu2receptor-dependent antidepressant actions

(2019) Panos Zanos et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Antidepressant-relevant concentrations of the ketamine metabolite (2R,6R)-hydroxynorketamine do not block NMDA receptor function

(2019) Eric W. Lumsden et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

( R )‐Ketamine exerts antidepressant actions partly via conversion to ( 2R,6R )‐hydroxynorketamine, while causing adverse effects at sub‐anaesthetic doses

(2019) Panos Zanos et al.   BRITISH JOURNAL OF PHARMACOLOGY

What role does the ( 2R,6R )‐hydronorketamine metabolite play in the antidepressant‐like and abuse‐related effects of ( R )‐ketamine?

(2019) Todd M. Hillhouse et al.   BRITISH JOURNAL OF PHARMACOLOGY

Pharmacological evaluation of clinically relevant concentrations of (2R,6R)-hydroxynorketamine

(2019) Christopher L. Shaffer et al.   NEUROPHARMACOLOGY

(2R,6R)-hydroxynorketamine rapidly potentiates hippocampal glutamatergic transmission through a synapse-specific presynaptic mechanism

(2019) Lace M. Riggs et al.   NEUROPSYCHOPHARMACOLOGY

Beneficial effects of (R)-ketamine, but not its metabolite (2R,6R)-hydroxynorketamine, in the depression-like phenotype, inflammatory bone markers, and bone mineral density in a chronic social defeat stress model

(2019) Zhongwei Xiong et al.   BEHAVIOURAL BRAIN RESEARCH

(R)-Ketamine Induces a Greater Increase in Prefrontal 5-HT Release Than (S)-Ketamine and Ketamine Metabolites via an AMPA Receptor-Independent Mechanism

(2019) Yukio Ago et al.   INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY

Pharmacologically diverse antidepressants facilitate TRKB receptor activation by disrupting its interaction with the endocytic adaptor complex AP-2

(2019) Senem Merve Fred et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Ketamine metabolite pilot study in a suicidal depression trial

(2019) Michael F. Grunebaum et al.   JOURNAL OF PSYCHIATRIC RESEARCH

Ketamine metabolite (2R,6R)-hydroxynorketamine enhances aggression via periaqueductal gray glutamatergic transmission

(2019) Lichao Ye et al.   NEUROPHARMACOLOGY

Ketamine-induced regulation of TrkB-GSK3β signaling is accompanied by slow EEG oscillations and sedation but is independent of hydroxynorketamine metabolites

(2019) Samuel Kohtala et al.   NEUROPHARMACOLOGY

Evaluation of the Wistar-Kyoto rat model of depression and the role of synaptic plasticity in depression and antidepressant response

(2019) Lily R. Aleksandrova et al.   NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS

Ketamine and Active Ketamine Metabolites Regulate STAT3 and the Type I Interferon Pathway in Human Microglia: Molecular Mechanisms Linked to the Antidepressant Effects of Ketamine

(2019) Ming-Fen Ho et al.   Frontiers in Pharmacology

Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression

(2018) Ming-Fen Ho et al.   BIOCHEMICAL PHARMACOLOGY

Stereochemical and structural effects of (2 R ,6 R )-hydroxynorketamine on the mitochondrial metabolome in PC-12 cells

(2018) Andréa T. Faccio et al.   BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

Common Neurotransmission Recruited in ( R , S )-Ketamine and (2 R ,6 R )-Hydroxynorketamine–Induced Sustained Antidepressant-like Effects

(2018) Thu Ha Pham et al.   BIOLOGICAL PSYCHIATRY

Mechanistic Target of Rapamycin–Independent Antidepressant Effects of ( R )-Ketamine in a Social Defeat Stress Model

(2018) Chun Yang et al.   BIOLOGICAL PSYCHIATRY

Enantioselective capillary electrophoresis provides insight into the phase II metabolism of ketamine and its metabolites in vivo and in vitro

(2018) Friederike A. Sandbaumhüter et al.   ELECTROPHORESIS

OUP accepted manuscript

(2018)   INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY

Functional organization of postsynaptic glutamate receptors

(2018) Nicky Scheefhals et al.   MOLECULAR AND CELLULAR NEUROSCIENCE

NMDAR-independent, cAMP-dependent antidepressant actions of ketamine

(2018) Nathan H. Wray et al.   MOLECULAR PSYCHIATRY

Mechanisms of ketamine action as an antidepressant

(2018) P Zanos et al.   MOLECULAR PSYCHIATRY

(2R,6R)-hydroxynorketamine rescues chronic stress-induced depression-like behavior through its actions in the midbrain periaqueductal gray

(2018) Dylan Chou et al.   NEUROPHARMACOLOGY

The Ketamine Metabolite 2R,6R-Hydroxynorketamine Blocks NMDA Receptors and Impacts Downstream Signaling Linked to Antidepressant Effects

(2018) Ege T Kavalali et al.   NEUROPSYCHOPHARMACOLOGY

(2R,6R)-Hydroxynorketamine is not essential for the antidepressant actions of (R)-ketamine in mice

(2018) Jun-ichi Yamaguchi et al.   NEUROPSYCHOPHARMACOLOGY

Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms

(2018) Panos Zanos et al.   PHARMACOLOGICAL REVIEWS

Lack of metabolism in (R)-ketamine’s antidepressant actions in a chronic social defeat stress model

(2018) Kai Zhang et al.   Scientific Reports

Lack of deuterium isotope effects in the antidepressant effects of (R)-ketamine in a chronic social defeat stress model

(2018) Kai Zhang et al.   PSYCHOPHARMACOLOGY

The novel antidepressant ketamine enhances dentate gyrus proliferation with no effects on synaptic plasticity or hippocampal function in depressive-like rats

(2018) Henrik Michaëlsson et al.   Acta Physiologica

Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants

(2018) Todd D. Gould et al.   Annual Review of Pharmacology and Toxicology

Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

(2018) Jaclyn N Highland et al.   JOURNAL OF PSYCHOPHARMACOLOGY

(2R,6R)-Hydroxynorketamine promotes dendrite outgrowth in human inducible pluripotent stem cell-derived neurons through AMPA receptor with timing and exposure compatible with ketamine infusion pharmacokinetics in humans

(2018) Ginetta Collo et al.   NEUROREPORT

Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine

(2018) Kenichi Fukumoto et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine

(2017) Yukihiko Shirayama et al.   INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY

Ketamine metabolites with antidepressant effects: Fast, economical, and eco-friendly enantioselective separation based on supercritical-fluid chromatography (SFC) and single quadrupole MS detection

(2017) Georg M. Fassauer et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Quantitative chiral and achiral determination of ketamine and its metabolites by LC–MS/MS in human serum, urine and fecal samples

(2017) Mahmoud Hasan et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Antidepressant Potential of ( R )-Ketamine in Rodent Models: Comparison with ( S )-Ketamine

(2017) Kenichi Fukumoto et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit

(2017) N Yao et al.   MOLECULAR PSYCHIATRY

Ketamine enhances structural plasticity in mouse mesencephalic and human iPSC-derived dopaminergic neurons via AMPAR-driven BDNF and mTOR signaling

(2017) L Cavalleri et al.   MOLECULAR PSYCHIATRY

Zanos et al. reply

(2017) Panos Zanos et al.   NATURE

Effects of a ketamine metabolite on synaptic NMDAR function

(2017) Kanzo Suzuki et al.   NATURE

Synthesis and N-Methyl-d-aspartate (NMDA) Receptor Activity of Ketamine Metabolites

(2017) Patrick J. Morris et al.   ORGANIC LETTERS

Possible role of the gut microbiota–brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model

(2017) Chun Yang et al.   Translational Psychiatry

Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance

(2016) Lesley K. Rao et al.   ANESTHESIOLOGY

A REVIEW OF KETAMINE ABUSE AND DIVERSION

(2016) Sean Sassano-Higgins et al.   DEPRESSION AND ANXIETY

Pharmacokinetics of ketamine and three metabolites in Beagle dogs under sevoflurane vs. medetomidine comedication assessed by enantioselective capillary electrophoresis

(2016) Friederike A. Sandbaumhüter et al.   JOURNAL OF CHROMATOGRAPHY A

Subchronic administration of (R,S)-ketamine induces ketamine ring hydroxylation in Wistar rats

(2016) R. Moaddel et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

(2016) Panos Zanos et al.   NATURE

Ketamine Metabolites Enantioselectively Decrease Intracellular D-Serine Concentrations in PC-12 Cells

(2016) Nagendra S. Singh et al.   PLoS One

Effects of medetomidine and its active enantiomer dexmedetomidine on N -demethylation of ketamine in canines determined in vitro using enantioselective capillary electrophoresis

(2015) Friederike A. Sandbaumhüter et al.   ELECTROPHORESIS

Microassay for ketamine and metabolites in plasma and serum based on enantioselective capillary electrophoresis with highly sulfated γ-cyclodextrin and electrokinetic analyte injection

(2015) Regula Theurillat et al.   ELECTROPHORESIS

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

(2015) C Yang et al.   Translational Psychiatry

(R,S)-Ketamine Metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine Increase the Mammalian Target of Rapamycin Function

(2014) Rajib K. Paul et al.   ANESTHESIOLOGY

EFFECTS OF KETAMINE ON EXPLICIT AND IMPLICIT SUICIDAL COGNITION: A RANDOMIZED CONTROLLED TRIAL IN TREATMENT-RESISTANT DEPRESSION

(2014) Rebecca B. Price et al.   DEPRESSION AND ANXIETY

The role of AMPA receptors in postsynaptic mechanisms of synaptic plasticity

(2014) Thomas E. Chater et al.   Frontiers in Cellular Neuroscience

Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept

(2013) Carolyn I Rodriguez et al.   NEUROPSYCHOPHARMACOLOGY

R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine

(2013) Ji-chun Zhang et al.   PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Relationship of Ketamine's Plasma Metabolites with Response, Diagnosis, and Side Effects in Major Depression

(2012) Carlos A. Zarate et al.   BIOLOGICAL PSYCHIATRY

Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment-resistant bipolar depression

(2012) Xiaochen Zhao et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

(2012) Ruin Moaddel et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Stereoselective and regiospecific hydroxylation of ketamine and norketamine

(2012) Zeruesenay Desta et al.   XENOBIOTICA

The role of BDNF in depression on the basis of its location in the neural circuitry

(2010) Hui Yu et al.   ACTA PHARMACOLOGICA SINICA

Enantioselective capillary electrophoresis for identification and characterization of human cytochrome P450 enzymes which metabolize ketamine and norketamine in vitro

(2010) Simone Portmann et al.   JOURNAL OF CHROMATOGRAPHY A

Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder

(2010) Nancy DiazGranados et al.   JOURNAL OF CLINICAL PSYCHIATRY

A parallel chiral–achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome

(2010) Ruin Moaddel et al.   TALANTA

Use of Human Microsomes and Deuterated Substrates: An Alternative Approach for the Identification of Novel Metabolites of Ketamine by Mass Spectrometry

(2009) S. C. Turfus et al.   DRUG METABOLISM AND DISPOSITION

CE provides evidence of the stereoselective hydroxylation of norketamine in equines

(2009) Andrea Schmitz et al.   ELECTROPHORESIS