Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions

Journal of Anesthesia and Translational Medicine, Год журнала: 2024, Номер 3(3), С. 65 - 75

Опубликована: Июль 11, 2024

Ketamine, a dissociative anesthetic, is widely utilized in both human and veterinary anesthesia. Its (S)-enantiomer, esketamine, similarly employed for anesthesia analgesia. The anesthetic effects of ketamine esketamine arise from their antagonism the N-methyl-D-aspartate receptor (NMDAR). In field psychiatry, rapid-acting antidepressant properties severe depression have generated significant interest, resulting its increased off-label usage United States (U.S.). 2019, nasal spray received approval use U.S. Europe. However, concerns emerged regarding potential adverse effects, including long-term efficacy, addiction risks, suicide risk clinical settings. contrast, arketamine, (R)-enantiomer ketamine, exhibits superior longer-lasting rodent models depression, with fewer side compared to esketamine. Nevertheless, research on efficacy safety arketamine patients remains limited. This article provides concise exploration historical two enantiomers while also delving into future directions application these fields.

Язык: Английский

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(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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Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-β1

Journal of Affective Disorders, Год журнала: 2024, Номер 367, С. 745 - 755

Опубликована: Сен. 3, 2024

Chronic restrain stress (CRS) induces depression-like behaviors and demyelination in the brain; however, relationship between these remains unclear. Arketamine, (R)-enantiomer of ketamine, has shown rapid antidepressant-like effects CRS-exposed mice. We examined whether arketamine can improve both brains Additionally, we investigated role transforming growth factor β1 (TGF-β1) beneficial arketamine. A single dose (10 mg/kg) improved behavior corpus callosum Correlations were found this region. Furthermore, pretreatment with RepSox, an inhibitor TGF-β1 receptor, significantly blocked on Finally, a intranasal administration ameliorated The precise mechanisms by which contributes to remain These data suggest that CRS-induced may contribute behaviors, mitigate changes through TGF-β1-dependent mechanism.

Язык: Английский

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Experimental evolution of a mammalian holobiont: selection for herbivorous capability in bank voles yields distinct and robust gut microbial communities

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 5, 2024

Background Symbiotic associations between animals and their microbiota are increasingly recognized as critical to the functioning of individuals evolution complex adaptations, such mammalian herbivory. This has led development "hologenome" theory evolution, which proposes that natural selection can act through a conglomerate biological unit, "holobiont" - host its associated microbiome. Although concept is appealing, merits debated, few attempts have been made test specific assumptions directly using experimental evolutionary approach. Results Here, we fill this gap lines bank vole (Myodes = Clethrionomys glareolus) selected for enhanced ability cope with low-quality herbivorous diet unselected control lines. In 4-day diet, juvenile voles from "herbivorous" maintained or increased body mass better than those had an rate food consumption. Results nature-nurture design, in combined dietary treatment cohabitation distinct (to allow horizontal bacterial transfer), showed harbored caecal microbiome altered composition structure, abundances several phyla genera, regardless origin cohabitant. differences were small, they partially robust changes housing conditions. Microbial characteristics also correlated selection-related traits at level individual variation. Conclusions These results, complementary cross-fostering experiment, microbial be treated organismal functional trait, largely determined by genetic background early maternal effects, change response acting on other traits. Such results consistent hologenomic evolution.

Язык: Английский

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Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice

Pharmacology Biochemistry and Behavior, Год журнала: 2024, Номер 245, С. 173906 - 173906

Опубликована: Ноя. 15, 2024

Язык: Английский

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