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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(12), С. 6804 - 6804

Опубликована: Июнь 20, 2024

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

Язык: Английский

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The vagus nerve: An old but new player in brain–body communication

Brain Behavior and Immunity, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis

Neurobiology of Disease, Год журнала: 2024, Номер 199, С. 106573 - 106573

Опубликована: Июнь 18, 2024

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors chronic social defeat stress (CSDS) model depression. This study investigated whether spleen contributes arketamine CSDS model. We found that splenectomy significantly inhibited arketamine's CSDS-susceptible mice. RNA-sequencing analysis identified oxidative phosphorylation (OXPHOS) pathway prefrontal cortex (PFC) as a key mediator splenectomy's impact on effects. Furthermore, oligomycin A, an inhibitor OXPHOS pathway, reversed suppressive Specific genes within pathways, such COX11, UQCR11 ATP5e, may contribute these inhibitory Notably, transforming growth factor (TGF)-β1, along with appears modulate Additionally, SRI-01138, agonist TGF-β1 receptor, alleviated Subdiaphragmatic vagotomy also counteracted These findings suggest PFC play significant roles arketamine, mediated through spleen-brain axis via vagus nerve.

Язык: Английский

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Depression-like phenotypes in mice with hepatic ischemia/reperfusion injury: A role of gut–microbiota–liver–brain axis via vagus nerve

Journal of Affective Disorders, Год журнала: 2023, Номер 345, С. 157 - 167

Опубликована: Окт. 24, 2023

Язык: Английский

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Beneficial effects of arketamine on the reduced bone mineral density in susceptible mice after chronic social defeat stress: Role of the gut–microbiota–bone–brain axis

Neuropharmacology, Год журнала: 2023, Номер 228, С. 109466 - 109466

Опубликована: Фев. 15, 2023

Язык: Английский

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A role of splenic heme biosynthesis pathway in the persistent prophylactic actions of arketamine in lipopolysaccharide-treated mice

Translational Psychiatry, Год журнала: 2023, Номер 13(1)

Опубликована: Июль 25, 2023

Relapse is common in remitted patients with major depressive disorder (MDD). Arketamine, an (R)-enantiomer of ketamine, has persistent prophylactic actions inflammatory model depression. However, the precise mechanisms underlying these remain unknown. Given role brain-spleen axis depression, we sought to identify splenic molecular targets that play a arketamine. Lipopolysaccharide (LPS) (1.0 mg/kg) was administered 6 days after single injection arketamine (10 or saline. RNA-sequencing analysis found altered expression heme biosynthesis II pathway. Quantitative RT-PCR revealed pretreatment blocked increased genes involved pathway LPS-treated mice, namely, 5-aminolevulinase synthase 2 (Alas2), ferrochelatase (Fech), hydroxymethylbilane (Hmbs). Interestingly, there were positive correlations between and spleen weight plasma levels pro-inflammatory cytokines. We also higher ALAS2 FECH from MDD patients. Pretreatment key intermediate precursor heme, 5-aminolaevulinic acid (300 mg/kg/day for 3 days), caused splenomegaly, cytokines, depression-like behavior low-dose LPS (0.1 mg/kg)-treated mice. inhibitor, succinyl acetone (120 had effects These data suggest novel inflammation-related Therefore, could be new target prevention relapse

Язык: Английский

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Pick fecal microbiota transplantation to enhance therapy for major depressive disorder

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2023, Номер 128, С. 110860 - 110860

Опубликована: Сен. 9, 2023

Язык: Английский

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A role of gut–brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress

Pharmacology Biochemistry and Behavior, Год журнала: 2024, Номер 238, С. 173736 - 173736

Опубликована: Фев. 23, 2024

Язык: Английский

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Subdiaphragmatic vagotomy reduces hypothalamic oxytocin expression and blood levels after oral MDMA administration in male rats

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2025, Номер 137, С. 111260 - 111260

Опубликована: Янв. 22, 2025

Язык: Английский

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Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application

Genes, Год журнала: 2024, Номер 15(4), С. 431 - 431

Опубликована: Март 29, 2024

Many investigations have evaluated the expression of noncoding RNAs (ncRNAs) as well their related molecular functions and biological machineries in individuals with alcohol dependence. Alcohol dependence may be one most prevailing psychological disorders globally, its pathogenesis is intricate inadequately comprehended. There substantial evidence indicating significant links between multiple genetic factors development In particular, critical roles ncRNAs been emphasized pathology mental illnesses, probably including comprehension action modification, furthermore, they emerged therapeutic targets for a variety psychiatric It worth mentioning that dysregulated has regularly detected An in-depth knowledge m6A modification valuable novel treatment against general, more profound understanding practical might make important contributions to precise diagnosis and/or actual management Here, this review, we mostly focused on up-to-date regarding alterations modifications Then, present prospects future research applications concept engram system.

Язык: Английский

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