Beyond NMDA Receptors: A Narrative Review of Ketamine’s Rapid and Multifaceted Mechanisms in Depression Treatment DOI Open Access

Z Antoś,

Xawery Żukow,

Laura Bursztynowicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13658 - 13658

Published: Dec. 20, 2024

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine's molecular actions. primarily works by antagonizing NMDA receptors, reducing GABAergic inhibition, increasing glutamate release. enhanced activates AMPA triggering crucial downstream cascades, including BDNF-TrkB mTOR pathways, promoting synaptic proliferation regeneration. Moreover, neuroimaging have demonstrated alterations in brain networks involved emotional regulation, Default Mode Network (DMN), Central Executive (CEN), Salience (SN), which are frequently disrupted depression. Despite promising findings, reveals significant inaccuracies gaps understanding full scope therapeutic potential. For instance, ketamine engages opioid insinuating a permissive role system amplifying effects, albeit does not operate direct agonist. Further exploration is requisite comprehensively ascertain safety profile, long-term efficacy, impact genetic determinants, such BDNF polymorphisms, treatment responsiveness.

Language: Английский

Beyond NMDA Receptors: A Narrative Review of Ketamine’s Rapid and Multifaceted Mechanisms in Depression Treatment DOI Open Access

Z Antoś,

Xawery Żukow,

Laura Bursztynowicz

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13658 - 13658

Published: Dec. 20, 2024

The rising prevalence of depression, with its associated suicide risk, demands effective fast-acting treatments. Ketamine has emerged as promising, demonstrating rapid antidepressant effects. While early studies show swift mood improvements, precise mechanisms remain unclear. This article aims to compile and synthesize the literature on ketamine's molecular actions. primarily works by antagonizing NMDA receptors, reducing GABAergic inhibition, increasing glutamate release. enhanced activates AMPA triggering crucial downstream cascades, including BDNF-TrkB mTOR pathways, promoting synaptic proliferation regeneration. Moreover, neuroimaging have demonstrated alterations in brain networks involved emotional regulation, Default Mode Network (DMN), Central Executive (CEN), Salience (SN), which are frequently disrupted depression. Despite promising findings, reveals significant inaccuracies gaps understanding full scope therapeutic potential. For instance, ketamine engages opioid insinuating a permissive role system amplifying effects, albeit does not operate direct agonist. Further exploration is requisite comprehensively ascertain safety profile, long-term efficacy, impact genetic determinants, such BDNF polymorphisms, treatment responsiveness.

Language: Английский

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