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Title:
Neurochemical Mechanisms Underlying the Rapid Antidepressant Action of Ketamine: https://go.tanurtravel.com/maryjomontague A Comprehensive Review
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Abstract
Ketamine, an N‑methyl‑D‑aspartate (NMDA) receptor antagonist, has emerged as a pioneering rapid‑acting antidepressant. Its therapeutic efficacy manifests within hours, contrasting starkly with the protracted onset of conventional monoaminergic agents. This review consolidates preclinical and clinical evidence elucidating ketamine’s neurochemical cascade: blockade of extrasynaptic NMDA receptors on GABAergic interneurons, resultant glutamate surge, AMPA receptor activation, BDNF release, downstream mTOR signaling, and synaptogenesis in the medial prefrontal cortex and hippocampus. We also discuss adjunctive pharmacotherapies—ketamine’s enantiomer esketamine, glycine modulators, and AMPA potentiators—that may amplify antidepressant response or mitigate side effects. Emerging data on biomarkers (e.g., CSF BDNF levels) and personalized approaches underscore the translational potential of this mechanistic framework.
Keywords: ketamine, esketamine, enantiomers, glutamate, AMPA receptors, mTOR pathway, synaptogenesis, depression, pharmacodynamics, therapeutic strategies.