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, Dennis S. Charney
The Annual Review of Pharmacology and Toxicology January 6, 2014 DOI: 10.1146/annurev-pharmtox-011613-135950 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Open-label Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine Serotonin Depression Esketamine |
| Keywords | Antidepressant Monoaminergic Pharmacology Nmda receptor Glutamate receptor Gsk-3 Hippocampus Kinase Anesthesia |
| Citations | 166 |
| Key findings | Ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression, mediated by mTOR, eEF2, and GSK-3. |
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.