Year-end Sale % OFF 
Abstract
Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, has been employed clinically as an intravenous anesthetic since the 1970s. More recently, ketamine has received attention for its rapid antidepressant effects and is actively being explored as a treatment for a wide range of neuropsychiatric syndromes. In model systems, ketamine appears to display a combination of neurotoxic and neuroprotective properties that are context dependent. At anesthetic doses applied during neurodevelopmental windows, ketamine contributes to inflammation, autophagy, apoptosis, and enhances levels of reactive oxygen species. At the same time, subanesthetic dose ketamine is a powerful activator of multiple parallel neurotrophic signaling cascades with neuroprotective actions that are not always NMDAR-dependent. Here, we summarize results from an array of preclinical studies that highlight a complex landscape of intracellular signaling pathways modulated by ketamine and juxtapose the somewhat contrasting neuroprotective and neurotoxic features of this drug.
Highlights
Over the past several years, ketamine has garnered significant interest as a novel therapeutic within the research and lay/media communities for its efficacy as a rapidly acting antidepressant
Autry et al (2011) showed that 3.0 mg/kg ketamine administered to mice with a conditional Bdnf -knockout failed to produce antidepressant-like effects. These findings suggest that the mammalian target of rapamycin (mTOR)/brainderived neurotrophic factor (BDNF) pathway, possibly through an NMDARindependent mechanism, is critical for the antidepressant-like effects of ketamine (Fukumoto et al, 2019)
Fan et al (2017) showed that subanesthetic ketamine injections (8 mg/kg) produced neuroprotective effects in a mouse model of Parkinson disease (PD), which corresponded with elevated expression of autophagy markers and reduced mTOR activation compared to untreated PD mice
Summary
Over the past several years, ketamine has garnered significant interest as a novel therapeutic within the research and lay/media communities for its efficacy as a rapidly acting antidepressant. As ketamine infusion protocols gradually become integrated into mainstream psychiatry practices (Sanacora et al, 2017), a large body of preclinical research, encompassing a range of model systems, has shed light on the complex pharmacodynamic landscape of ketamine, which extends well beyond N-methyl-D-aspartate receptor (NMDAR) antagonism. A growing body of research seeks to identify one or more biologically active metabolites of ketamine (Zanos et al, 2016) or agents with similar pharmacodynamic properties (Kang et al, 2017) that may avoid psychotomimetic and cardiovascular side effects (Zanos et al, 2016). We summarize a body of basic science literature to provide a forecast about ketamine’s potential as a neuroprotective agent (defined as a treatment that promotes glial/neuronal health during adversity), as well as clarify ketamine’s cellular actions that may cause it to function as a neurotoxic agent (resulting in adverse neuronal/glial health or cell death)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
