The antidepressant actions of ketamine and its enantiomers

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 246, P. 108431 - 108431

Published: May 4, 2023

Language: Английский

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Effects of perioperative use of esketamine on postpartum depression risk in patients undergoing cesarean section: A randomized controlled trial

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 339, P. 815 - 822

Published: July 22, 2023

Postpartum depression (PPD) is a prevalent public health issue. Although ketamine has prophylactic effects on PPD in women undergoing cesarean section, the of esketamine remain unclear. This trial aimed to evaluate efficacy perioperative infusion risk by assessing Edinburgh Postnatal Depression Scale (EPDS) scores and blood biomarkers.A total 150 participants elective section were randomly allocated receive either or normal saline. Since 27 excluded due consent withdrawal loss follow-up, 123 patients included. The primary outcome was prevalence risk. Secondary outcomes included postpartum anxiety (PPA) risk, levels biomarkers, postoperative pain intensity, cumulative sufentanil consumption.The PPA at 3 days, 42 months, 6 months did not differ between two groups. Furthermore, EPDS scores, intensity rest, during coughing days (POD) 1 2 Sufentanil consumption 0-12 h, 12-24 0-24 0-48 h postoperatively significantly lower group compared control group. Blood biomarkers groups POD 3.The sample size small. simply screened, diagnosed.Perioperative administration decrease incidence after section. However, reduced opioid consumption.

Language: Английский

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Inflammation, stress and depression: An exploration of ketamine’s therapeutic profile

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(4), P. 103518 - 103518

Published: Feb. 8, 2023

Language: Английский

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Caspase-1 affects chronic restraint stress-induced depression-like behaviors by modifying GABAergic dysfunction in the hippocampus

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 27, 2023

Abstract Major depression disorder (MDD) is one of the most common psychiatric disorders and leading causes disability in worldwide. Both inflammation GABAergic dysfunction have been implicated pathophysiology MDD. Caspase-1, a classic inflammatory caspase, regulates AMPARs-mediated glutamatergic neurotransmission. However, role caspase-1 chronic stress-induced remains largely unknown. In this study, we found that serum hippocampal caspase-1-IL-1β levels increased significantly restraint stress (CRS) mice, significant negative correlation occurred between depression-like behaviors. Furthermore, CRS decreased GAD67 mRNA neurotransmission accompanied by reduction GABA concentration, reduced amplitude frequency mIPSCs inhibitory postsynaptic currents (mIPSCs) surface expression A Rs γ2 subunit hippocampus. Genetic deficiency not only blocked CRS-induced behaviors, but also alleviated impairments Finally, reexpression hippocampus Caspase-1 −/− mice susceptibility to anxiety- behaviors through inhibiting Rs-mediated synaptic transmission. Our study suggests dysregulates via increasing caspase-1-mediated neuroinflammation hippocampus, ultimately This work illustrates targeting may provide potential therapeutic benefits stress-related pathogenesis

Language: Английский

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

Journal of Anesthesia and Translational Medicine, Journal Year: 2024, Volume and Issue: 3(3), P. 65 - 75

Published: July 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.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6804 - 6804

Published: June 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.

Language: Английский

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Role of the gut–brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 189, P. 106348 - 106348

Published: Nov. 11, 2023

3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated effects subdiaphragmatic vagotomy (SDV) modulating mice subjected chronic restrain (CRS). Pretreatment (10 mg/kg/day for 14 days) blocked anhedonia-like behavior reduced expression synaptic proteins brain-derived neurotrophic factor prefrontal cortex (PFC) CRS-exposed Interestingly, SDV beneficial on these alterations Analysis gut microbiome revealed four measures α-diversity between sham + CRS group group. Moreover, specific microbes differed vehicle group, differences microbial composition were observed all groups. Untargeted metabolomics analysis showed prevented increase plasma levels three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] positive correlations found two abundance several across In conclusion, our data suggest via vagus nerve might MDMA.

Language: Английский

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Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 11, 2024

( R , S )- and )-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) become a research focus recent years. However, they both risks psychomimetic effects, dissociative abuse liability, which limit their clinical use. Recent preclinical studies shown that has more efficient lasting antidepressant effect with fewer side effects compared to )-ketamine. small-sample randomized controlled trial found although lower incidence adverse reactions adult TRD treatment, its efficacy is not superior placebo group, indicating advantage still needs further verification clarification. Moreover, an increasing body suggests might also applications prevention medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson’s disease, multiple sclerosis, osteoporosis, substance use inflammatory diseases, COVID-19, organophosphate poisoning. This article briefly reviews mechanism action on antidepressants related )-ketamine, fully revealing application potential development prospects, providing some references assistance for subsequent expanded research.

Language: 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, Journal Year: 2024, Volume and Issue: 367, P. 745 - 755

Published: Sept. 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.

Language: Английский

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Epigenetic mechanisms of rapid-acting antidepressants

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 4, 2024

Language: Английский

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