Paper
(2R,6R)-hydroxynorketamine rapidly potentiates hippocampal glutamatergic transmission through a synapse-specific presynaptic mechanism
Published Jun 19, 2019 · L. Riggs, Y. Aracava, P. Zanos
Neuropsychopharmacology
Q1 SJR score
41
Citations
1
Influential Citations
Abstract
Abstract hidden due to publisher request; this does not indicate any issues with the research. Click the full text link above to read the abstract and view the original source.
In Vitro Study
Very Rigorous JournalStudy Snapshot
(2R,6R)-hydroxynorketamine enhances hippocampal glutamatergic transmission through a concentration-dependent, NMDAR-independent, and synapse-selective increase in glutamate release probability without directly affecting AMPAR function.
PopulationOlder adults (50-71 years)
Sample size24
MethodsObservational
OutcomesBody Mass Index projections
ResultsSocial networks mitigate obesity in older groups.
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References
Pharmacological evaluation of clinically relevant concentrations of (2R,6R)-hydroxynorketamine
Ketamine's antidepressant effects require increased GluA1 expression, but its metabolite (2R,6R)-hydroxynorketamine (HNK) does not directly activate AMPARs, and its pharmacokinetics are not fully understood.
2019·25citations·C. L. Shaffer et al.·Neuropharmacology
Neuropharmacology
Antidepressant-relevant concentrations of the ketamine metabolite (2R,6R)-hydroxynorketamine do not block NMDA receptor function
Antidepressant-relevant concentrations of (2R,6R)-hydroxynorketamine do not block NMDA receptor function, suggesting alternative molecular targets for novel rapid antidepressant drugs.
2019·125citations·E. Lumsden et al.·Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine
The antidepressant effects of (2R,6R)-hydroxynorketamine require activity-dependent release of BDNF and increased synaptic function in the medial prefrontal cortex, highlighting its potential as a new treatment for depression.
2018·149citations·K. Fukumoto et al.·Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine
(2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy after oral administration in mice.
2018·43citations·Jaclyn N. Highland et al.·Journal of Psychopharmacology
Journal of Psychopharmacology
Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments
Ketamine and other glutamate-based treatments show potential for rapid-acting antidepressant effects in treatment-resistant depression without dissociative side effects.
2018·120citations·B. Kadriu et al.·International Journal of Neuropsychopharmacology
International Journal of Neuropsychopharmacology
Citations
Rapid Hippocampal Synaptic Potentiation Induced by Ketamine Metabolite (2R,6R)-Hydroxynorketamine Persistently Primes Synaptic Plasticity
The ketamine metabolite HNK rapidly stimulates hippocampal synaptic efficacy, leading to persistent antidepressant-relevant plasticity, potentially offering new antidepressant targets.
2024·0citations·Kyle A. Brown et al.·bioRxiv
bioRxiv
(2R, 6R)-hydroxynorketamine ameliorates PTSD-like behaviors during the reconsolidation phase of fear memory in rats by modulating the VGF/BDNF/GluA1 signaling pathway in the hippocampus
(2R,6R)-hydroxynorketamine improves PTSD-like behaviors during the reconsolidation phase of fear memory in rats, potentially offering a new target for clinical treatment and prevention of fear-related disorders.
2024·0citations·Han Wang et al.·Behavioural Brain Research
Behavioural Brain Research
A Phase 1 Assessment of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (2R,6R)-Hydroxynorketamine in Healthy Volunteers.
RR-HNK is well-tolerated and has an acceptable pharmacokinetic profile, supporting its progression into Phase 2 clinical trials for mental health disorders.
2024·1citation·S. Raja et al.·Clinical pharmacology and therapeutics
Clinical pharmacology and therapeutics
A molecular perspective on mGluR5 regulation in the antidepressant effect of ketamine.
Ketamine's antidepressant effects may be linked to mGluR5 regulation, which may involve NMDAR inhibition and mGluR5 modulation.
2024·3citations·Ola Sobhy A. Elmeseiny et al.·Pharmacological research
Pharmacological research
(2R,6R)-hydroxynorketamine facilitates extinction and prevents emotional impairment and stress-induced reinstatement in morphine abstinent mice
(2R,6R)-hydroxynorketamine shows potential as a next-generation pharmacotherapy for opioid use disorders by addressing emotional disturbances associated with protracted abstinence.
2023·1citation·Andria Michael et al.·bioRxiv
bioRxiv
A synopsis of multitarget therapeutic effects of anesthetics on depression.
Anesthetic drugs like ketamine, isoflurane, N2O, and propofol show potential in rapidly improving depression symptoms and promoting long-term effects.
2023·0citations·Guowei Wu et al.·European journal of pharmacology
European journal of pharmacology