(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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Attenuating Ketamine-Induced Nephrotoxicity with Bryophyllum pinnatum Extract: Biochemical and Histological Investigation

Journal of Complementary and Alternative Medical Research, Journal Year: 2025, Volume and Issue: 26(1), P. 21 - 36

Published: Jan. 4, 2025

Background: Ketamine, a widely used anesthetic agent, has been shown to induce nephrotoxicity, characterized by increased kidney function markers and structural damage. Despite its therapeutic applications, the adverse effects of ketamine on kidneys necessitate exploration potential protective agents. Bryophyllum pinnatum (B. pinnatum), an herbal plant with long history medicinal use, demonstrated various properties, including antioxidant, anti-inflammatory, nephroprotective effects. However, role in mitigating ketamine-induced damage remains inadequately explored. Methods: Sixty male Wistar rats were assigned six groups. Group 1 served as control, while 2 received (20 mg/kg) for 7 days renal toxicity. Groups 3-6 treated plus different doses B. extract (50, 100, 200 21 days. Biochemical markers, blood urea nitrogen (BUN), creatinine, urea, sodium (Na), potassium (K), measured, histopathological evaluations conducted tissues. Results: Ketamine administration significantly BUN (11.50±0.17 mg/dL), creatinine (100.00±2.89 µmol/L), (43.00±2.08 Na (164.00±4.16 mmol/L), K (2.83±0.34 mmol/L) compared controls (p<0.05). Treatment at 100 mg/kg reduced these biomarkers, highest dose showing values near control levels (BUN: 5.33±0.24 mg/dL, creatinine: 64.67±4.26 µmol/L, urea: 12.23±0.15 Na: 131.00±0.58 mmol/L, K: 1.10±0.07 p<0.05). Histologically, treatment attenuated damage, marked improvements tissue architecture. Conclusion: exhibited significant effects, evidenced reduction biomarkers improved histological features, suggesting agent managing

Language: Английский

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Disruptions in cellular communication: Molecular interplay between glutamate/NMDA signalling and MAPK pathways in neurological disorders

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Evolution of Alzheimer’s Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 128 - 128

Published: Jan. 17, 2025

Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among elderly and profoundly impairing their quality life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, memantine, offer only modest symptomatic relief are frequently associated with significant adverse effects. Faced this challenge in line advances understanding pathophysiology neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge underlying pathophysiological mechanisms disease. Among alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target eliminate toxic proteins implicated AD. Additionally, use medicinal plants is examined, synergistic effects components may confer neuroprotective properties. The modulation gut microbiota also addressed a peripheral strategy that could influence neuroinflammatory degenerative processes brain. Furthermore, potential emerging approaches, microRNAs regulate key cellular nanotherapy, which enables precise drug delivery central nervous system, analyzed. Despite promising these strategies, incidence continues rise. Therefore, it proposed achieving effective treatment future require integration combined maximizing different interventions.

Language: Английский

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The spectrum-efficacy correlation of Kai-Xin-San for cognition of Aβ42 transgenic Drosophila and verification of its active ingredients

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 28, 2025

Introduction This study aims to establish the fingerprint spectra of Kai-Xin-San (KXS) and investigate its spectrum-effect relationship in treating Alzheimer’s disease (AD). Methods Initially, fingerprints 15 batches KXS were established analyzed using HPLC, with method’s precision, stability, repeatability thoroughly evaluated. Subsequently, effects assessed an olfactory escape memory experiment, utilizing Aβ 42 transgenic drosophila as a model. Finally, between improvement was analyzed, active ingredients subjected validation testing. Results The results identified seventeen common peaks fingerprint, eight components determined: polygalaxanthone III, 3-6-disinapoylsucrose, ginsenoside Rg1, Rb1, β-asarone, α-asarone, dehydrotumulosic acid, dehydropachymic acid. Treatment (1%, for 4 days) significantly enhanced performance index flies experiment. Both analysis tests indicated that α-asarone positively correlated improved HPLC method demonstrated excellent accuracy, reproducibility, making it suitable quality evaluation control KXS. Polygalaxanthone are potential anti-AD effects. Discussion These findings provide experimental basis developing new drugs based on ingredient combinations.

Language: Английский

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Future Perspectives of NMDAR in CNS Disorders

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 877 - 877

Published: Feb. 14, 2025

Neurodegenerative diseases such as Alzheimer's and Parkinson's are among the leading causes of physical cognitive disability across globe. Fifty million people worldwide suffer these diseases, that number is expected to rise population ages. Ictus another pathology also courses with neurodegeneration a cause mortality long-term in developed countries. Schizophrenia not common other mental disorders, affecting approximately 24 worldwide. All disorders have still there an effective pharmacological treatment cure them. The N-methyl-D-aspartate (NMDA) receptor (NMDAR) has attracted attention potential therapeutic target due its important role learning memory implication excitotoxicity processes. Some drugs targeting NMDARs already being used treat symptoms central nervous system (CNS). Here, we aim review implications NMDAR CNS pathologies, target, future perspectives for developing new treatments focused on receptors.

Language: Английский

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Acute subanesthetic ketamine-induced effects on the mismatch negativity and their relationship to early and sustained treatment response in major depressive disorder

Journal of Psychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Background: A sub-anesthetic dose of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, produces robust antidepressant effects in treatment-resistant major depressive disorder (MDD). The mismatch negativity (MMN) is reliant on glutamatergic neurotransmission and reduced by NMDAR antagonists. MMN may characterise the neural mechanisms underlying ketamine’s effects. Aims: This study examined acute ketamine midazolam its relationship to early sustained decreases symptoms. Methods: Treatment-resistant MDD patients ( N = 24), enrolled a multi-phase clinical trial, received two intravenous infusions within initial double-blind crossover phase: (0.5 mg/kg) (30 μg/kg). Three recordings were carried out per session (pre-, immediately post- 2 h post-infusion). Peak amplitude (μV), latency (ms), theta event-related oscillations (EROs), phase locking factor (PLF) source-localised generator activity assessed. Relationships between changes indices (Phase 1: double-blind, cross-over phase) (Phases 2, 3: open-label repeated maintenance phases, respectively) symptoms (Montgomery-Åsberg Depression Rating Scale score) examined. Results: Ketamine frontal amplitudes, ERO post-infusion peak activity. Select baseline ketamine-induced correlated predicted greater (left ERO, left PLF) (baseline PLF, right inferior temporal activity) symptom reductions. Conclusions: Acute NMDARs blockade MMN, with larger reductions predicting improvement. serve as non-invasive biomarker response agents.

Language: Английский

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Intranasal Delivery of Lithium Salt Suppresses Inflammatory Pyroptosis in the Brain and Ameliorates Memory Loss and Depression-like Behavior in 5XFAD Mice

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 17, 2025

Abstract Background Alzheimer’s disease (AD) is a devastating neurodegenerative and has no treatment that can cure or halt the progression. This study explored therapeutic potential of lithium salt dissolved in Ryanodex formulation vehicle (RFV) delivered to brain by intranasal application. We first compared concentrations blood wild-type mice following oral administration chloride (LiCl) either RFV water. The beneficial side effects versus LiCl these were assessed mechanisms underlying efficacy anti-inflammation anti-pyroptosis brains also investigated both 5XFAD Disease brains. Methods For concentrations, (WT) B6SJLF1/J at 2 months age treated with (3 mmol/kg) Brain measured various times after drugs administration. Brain/blood concentration ratios then determined. studying their mechanisms, WT daily, Monday Friday each week, beginning 9 12-week duration. Animal behaviors for depression (tail suspension), cognition (fear conditioning Y maze), olfaction (buried food test), motor functions (rotarod) 5 12 months. Blood tissue harvested from 13 biomarkers thyroid (thyroid stimulating hormone, TSH) kidney (creatinine) using ELISA. Changes protein expression levels endoplasmic reticulum Ca 2+ release channels type 1 InsP 3 receptors (InsP R-1), malondialdehyde (MDA)-modified proteins 4-hydroxy-2-nonenal (4-HNE), pyroptosis regulatory (NLR family pyrin domain containing (NLRP3), cleaved caspase-1, N-terminal Gasdermin D (GSDMD)), cytotoxic (IL-1β, IL-18, IL-6, TNF-α) cytoprotective (IL-10) cytokines synapse (PSD-95, synapsin-1) determined immunoblotting. Mouse body weights monitored regularly. Results Compared nanoparticles, markedly decreased time range 30–120 min. ratio brain/blood significantly increased, comparison those Intranasal inhibited memory loss depressive behavior adult aged mice. Additionally effectively suppressed increases R-1, intracellular oxidative stress markers (4-HNE-bound MDA-modified proteins), activation (NLRP3, GSDMD) TNF-α), but reversed down-regulation cytokine IL-10. alleviated postsynaptic PSD-95, not synapsin-1, level function marker creatinine was increased than an age-dependent manner this elevation abolished delivery RFV. weeks did affect function, nor it smell muscle weight. Conclusion ratio, its robustly protected against depressive-like behavior, while had concerning toxicity These lithium-induced strongly associated lithium’s suppression R-1 channel receptor increase, pathological neuroinflammation pathway, as well synaptic PSD-95. could become effective potent inhibitor inflammation/pyroptosis CNS serve new AD-associated dementia minimal unwanted including peripheral organ toxicity. Graphical Formulation Vehicle cognitive dysfunction depression-like mice, on functions. I InsP3 (InsP3R-1) Ca2+ proteins, stress, pathway (Increased NLRP3, GSDMD, IL-1β IL-18). drug treating AD.

Language: Английский

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Unveiling exosomal biomarkers in neurodegenerative diseases: LC-MS-based profiling

Extracellular Vesicle, Journal Year: 2025, Volume and Issue: 5, P. 100071 - 100071

Published: March 22, 2025

Language: Английский

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Neuro–astrocytic network in breast cancer brain metastases: Adaptive mechanisms and novel therapeutic targets

International Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Breast cancer brain metastases (BrM) are a common and fatal complication in advanced breast patients, with the intricate microenvironment significantly limiting efficacy of current therapeutic strategies. Recently, neuro-astrocytic network, as core component metastasis microenvironment, has garnered extensive attention for its pivotal role supporting tumor adaptive growth. This review systematically outlines mechanisms network BrM, including bidirectional interactions between cells, neurons, astrocytes, their profound effects on synapse-like signaling, metabolic pathways, regulatory networks. Furthermore, we integrate recent advancements exploring targets discuss potential intervention strategies against tumor-microenvironment associated challenges. Future research focusing multi-target collaborative within this clinical translational may provide new avenues precise treatment BrM.

Language: Английский

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