1932

Abstract

The -methyl--aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on () prolonging/maintaining ketamine's antidepressant effects, () developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and () identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.

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/content/journals/10.1146/annurev-pharmtox-011613-135950
2014-01-06
2024-04-21
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  • Article Type: Review Article
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