Ketamine: Neuroprotective or Neurotoxic?

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.

Automated summary

Ketamine, a non-competitive NMDAR antagonist, has been used as an intravenous anesthetic since the 1970s and is now being explored for its rapid antidepressant effects in treating various neuropsychiatric syndromes. Studies have shown that ketamine exhibits both neurotoxic and neuroprotective properties depending on the context, affecting intracellular signaling pathways in complex ways. It acts as a powerful activator of neurotrophic signaling cascades at subanesthetic doses, showcasing contrasting neuroprotective and neurotoxic characteristics.