(, )- and ()-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that ()-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (, )- and ()-ketamine. However, a recent small-sample randomized controlled trial found that although ()-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that ()-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to ()-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.
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http://dx.doi.org/10.3389/fphar.2024.1337749 | DOI Listing |
The current state of mental health treatment for individuals diagnosed with major depressive disorder leaves billions of individuals with first-line therapies that are ineffective or burdened with undesirable side effects. One major obstacle is that distinct pathologies may currently be diagnosed as the same disease and prescribed the same treatments. The key to developing antidepressants with ubiquitous efficacy is to first identify a strategy to differentiate between heterogeneous conditions.
View Article and Find Full Text PDFAnesthetic and sedative drugs are small compounds known to bind to hundreds of proteins. One intriguing binding partner of propofol is the kinesin motor domain, kif5A, a neuronal mitochondrial transport protein. Here, we used zebrafish WT and kif5Aa KO larval behavioral assays to assess anesthetic sensitivity and combined that with zebrafish primary neuronal cell culture to probe for alteration in mitochondrial motility.
View Article and Find Full Text PDFBr J Psychiatry
January 2025
Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, Australia.
Background: Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.
Aims: To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.
World J Biol Psychiatry
January 2025
P1vital, Wallingford, UK.
Objectives: While neuropsychological effects of conventional antidepressants are well-documented, more research is needed for rapid-acting antidepressants. This study examines the effects of esketamine on emotion processing and cognitive functioning, both acutely and sub-chronically.
Methods: Eighteen treatment-resistant depression (TRD) patients received repeated intravenous esketamine infusions.
Inflamm Res
January 2025
Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Background: Mitochondrial dysfunction and damage can result in the release of mitochondrial DNA (mtDNA) into the cytoplasm, which subsequently activates the cGAS-STING pathway, promoting the onset of inflammatory diseases. Various factors, such as oxidative stress, viral infection, and drug toxicity, have been identified as inducers of mitochondrial damage. This study aims to investigate the role of mtDNA as a critical inflammatory mediator in the pathogenesis of ketamine (KET)-induced cystitis (KC) through the cGAS-STING pathway.
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