Ketamine and its metabolites: Potential as novel treatments for depression

Hashimoto, Kenji; Chaki, Shigeyuki

doi:10.1016/j.neuropharm.2023.109492

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…The resultant enhancement of excitatory neurotransmission and the induction of neurotrophic factors associated with antidepressant effects have been a long-standing mechanistic model. The ideas of non-NMDA mechanisms of action derive from a number of sources that include the potential for metabolites (non-NMDAR antagonists) to produce the antidepressant-like effects of ketamine [ 24 , 88 , 89 ] and data associating a number of non-NMDAR mechanisms of ketamine with its antidepressant efficacy [ 90 ] ( Section 7 ).…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

Shafique,

Demers,

Biesiada

et al. 2024

IJMS

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NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of (R)-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than (S)-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of (R)-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with (R)-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.

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Section: Mechanisms Of Actionmentioning

confidence: 99%

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

Shafique,

Demers,

Biesiada

et al. 2024

IJMS

View full text Add to dashboard Cite

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“…Such microbiota-centered perspective could potentially improve antidepressant efficacy in clinical practice. The antidepressant effects of ketamine have received increasing attention since the United States Food and Drug Administration approved (S)-ketamine nasal spray in March 2019 [151,152]. Zhou et al analyzed changes in lipid compositions in mice with induced chronic variable stress (CVS) and found that disruption of sphingolipids, glycerolipids, and fatty acyls was partially corrected by administration of (S)-ketamine [113].…”

Section: Western Medicinesmentioning

confidence: 99%

Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research

Liu,

Ma,

et al. 2023

Molecules

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Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker signatures at the metabolite level. In this comprehensive review, recent developments of MS-based metabolomics in MDD research are summarized from the perspective of analytical platforms (liquid chromatography-MS, gas chromatography-MS, supercritical fluid chromatography-MS, etc.), strategies (untargeted, targeted, and pseudotargeted metabolomics), key metabolite changes (monoamine neurotransmitters, amino acids, lipids, etc.), and antidepressant treatments (both western and traditional Chinese medicines). Depression sub-phenotypes, comorbid depression, and multi-omics approaches are also highlighted to stimulate further advances in MS-based metabolomics in the field of MDD research.

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Comparing presumptive with direct-to-definitive drug testing in oral fluid vs. urine for a U.S. national sample of individuals misusing drugs

Magura,

Lee-Easton,

Abu-Obaid

et al. 2023

Drug and Alcohol Dependence

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Ketamine and its metabolites: Potential as novel treatments for depression

Cited by 5 publications

References 31 publications

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders

Recent Progress in Mass Spectrometry-Based Metabolomics in Major Depressive Disorder Research

Comparing presumptive with direct-to-definitive drug testing in oral fluid vs. urine for a U.S. national sample of individuals misusing drugs

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