期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 54
卷 54, 期 -, 页码 119-139出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-011613-135950
关键词
NMDA receptor antagonist; rapid-acting antidepressants; major depressive disorder; bipolar depression; preclinical models of depression; mammalian target of rapamycin; mTOR
资金
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002857] Funding Source: NIH RePORTER
- Intramural NIH HHS [ZIA MH002857-09] Funding Source: Medline
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.
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