An update on ketamine and its two enantiomers as rapid-acting antidepressants
@article{Zhang2018AnUO, title={An update on ketamine and its two enantiomers as rapid-acting antidepressants}, author={Kai Zhang and Kenji Hashimoto}, journal={Expert Review of Neurotherapeutics}, year={2018}, volume={19}, pages={83 - 92} }
ABSTRACT Introduction: Depression is one of the most disabling diseases worldwide. Approximately one-third of depressed patients are treatment-resistant to the currently available antidepressants and there is a significant therapeutic time lag of weeks to months. There is a clear unmet need for rapid-acting and more efficacious treatments. (R,S)-ketamine, an old anesthetic drug, appears now to be going through a renaissance. Areas covered: This paper reviews recent literature describing the…
65 Citations
Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective
- Biology, PsychologyPsychiatry and clinical neurosciences
- 2019
The author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamines and discusses the other potential rapid‐acting antidepressant candidates to compare them with ketamine.
Antidepressant Actions of Ketamine and Its Two Enantiomers
- Biology, PsychologyKetamine
- 2020
Recent findings on the antidepressant actions of two enantiomers of ketamine are discussed, including (R,S), which has been reported to have a greater potency and longer-lasting antidepressant effects than (S)-ketamine in rodent models of depression.
Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine.
- Psychology, BiologyBiochemical pharmacology
- 2020
Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers
- Biology, PsychologyTherapeutic advances in psychopharmacology
- 2020
An overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers for predicting response to and/or monitoring of therapeutic outcome with ketamine is provided.
Repurposing of Drugs-The Ketamine Story.
- Psychology, BiologyJournal of medicinal chemistry
- 2020
Repurposing of ketamine for treating TRD provided a new understanding of the pathophysiology of depression-a paradigm shift from monoamine to glutamatergic neurotransmission, thus making it a unique tool to investigate the brain and its complex neurocircuitries.
Emergence of Ketamine as a Rapid Acting Antidepressant: Mechanistic Insights and Future Directions
- Biology, PsychologyKetamine Revisited - New Insights into NMDA Inhibitors [Working Title]
- 2021
This chapter will shed light on the various mechanisms of ketamine related to antidepressant activity, its pharmacokinetics, toxicology and ongoing clinical trials will also be discussed.
An update on NMDA antagonists in depression
- Psychology, BiologyExpert review of neurotherapeutics
- 2019
The present review aims to summarize and provide an update on published preclinical data evaluating the antidepressant efficacy of various NMDA antagonists and their mechanisms of action based on published results from clinical studies.
Ketamine: Leading us into the future for development of antidepressants
- Psychology, BiologyBehavioural Brain Research
- 2020
Rapid-Acting Antidepressants.
- Biology, MedicineCurrent pharmaceutical design
- 2018
The preclinical and clinical literature strongly suggests that rapid-acting antidepressants are the current focus of antidepressant drug discovery, and promising clinical findings exist for several compounds including ketamine and other NMDA receptor antagonists, scopolamine, and psilocybin.
References
SHOWING 1-10 OF 109 REFERENCES
Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide
- Biology, PsychologyF1000Research
- 2018
The discovery of ketamine and its unique mechanisms heralds a new era with tremendous promise for the development of novel, rapid, and efficacious antidepressant medications.
NMDAR inhibition-independent antidepressant actions of ketamine metabolites
- Psychology, BiologyNature
- 2016
It is shown that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice.
Letter to the Editor: R-ketamine: a rapid-onset and sustained antidepressant without risk of brain toxicity
- Psychology, BiologyPsychological Medicine
- 2016
The authors examined the time trajectory of efficacy of ketamine and non-ketamine NMDA-R antagonists in patients with major depressive disorder (MDD) and bipolar disorder and reported that R-ketamines showed greater potency and longer-lasting antidepressant effects than esketamine in animal models of depression.
Rapid Antidepressant Activity of Ketamine Beyond NMDA Receptor
- Biology, Psychology
- 2017
It is unlikely that NMDA receptor has a major role in the longer-lasting antidepressant effects of (R)-ketamine, although antagonism at this receptor may promote its rapid antidepressant activity.
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
- Psychology, MedicineArchives of general psychiatry
- 2006
Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.
The R-Stereoisomer of Ketamine as an Alternative for Ketamine for Treatment-resistant Major Depression
- Psychology, BiologyClinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
- 2014
Analysis of the primary outcome measure showed that the ketamine group experienced greater improvement in terms of Montgomery-Asberg depression rating scale (MADRS) scores than did the midazolam group, and data suggest that the R-stereoisomer of ketamine would be an alternative antidepressant for ketamine as R-ketamine may be free of psychotomimetic side effects.
Is (S)-norketamine an alternative antidepressant for esketamine?
- Psychology, BiologyEuropean Archives of Psychiatry and Clinical Neuroscience
- 2018
It seems that the effects of intranasal esketamine may be less potent than intravenous (R,S)-ketamine, which could be a safer antidepressant in humans than esketamines.
R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects
- Psychology, BiologyTranslational Psychiatry
- 2015
In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamines (esketamine), and findings suggest that, unlike S- ketamine, R -ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3.
Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Antidepressant Efficacy of Ketamine in Depressed Patients
- Psychology, MedicineBiological Psychiatry
- 2012
Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine
- Psychology, BiologyThe Journal of Pharmacology and Experimental Therapeutics
- 2017
This study is the first to demonstrate that (R)-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants, and confirmed the previous findings that ( R)-ketamines exerted longer-lasting antidepressant effects than (S-ketamine in animal models of depression.