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Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds
Journal article   Peer reviewed

Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other Compounds

Mark J Niciu, Ioline D Henter, David A Luckenbaugh, Carlos A Zarate and Dennis S Charney
Annual review of pharmacology and toxicology, Vol.54(1), pp.119-139
2014
DOI: 10.1146/annurev-pharmtox-011613-135950
PMCID: PMC4089991
PMID: 24392693

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Abstract

The N -methyl- d -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 ( a ) prolonging/maintaining ketamine’s antidepressant effects, ( b ) developing more selective NMDA receptor antagonists free of ketamine’s adverse effects, and ( c ) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine’s antidepressant effects.
bipolar depression preclinical models of depression mammalian target of rapamycin major depressive disorder rapid-acting antidepressants NMDA receptor antagonist mTOR

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