Journal
EXPERT REVIEW OF NEUROTHERAPEUTICS
Volume 11, Issue 1, Pages 33-36Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/ERN.10.176
Keywords
AMPA receptor; brain-derived neurotrophic factor (BDNF); cancer; ketamine; mTOR; NMDA receptor; protein synthesis; sigma-1 receptor; treatment-resistant depression
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Some patients with major depressive disorder remain resistant to antidepressant medication. A randomized, placebo-controlled, double-blind trial demonstrated that a single subanesthetic dose (0.5 mg/kg) of the N-methyl-D-aspartate receptor antagonist ketamine caused a rapid antidepressant effect within hours in treatment-resistant patients with major depressive disorder. However, the precise cellular mechanisms underlying ketamine's rapid antidepressant actions were unclear, although it is proposed that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor might be involved in these mechanisms. Recently, Li et al. reported the role of the mammalian target of rapamycin (mTOR) signaling pathway, a ubiquitous protein kinase involved in protein synthesis and synaptic plasticity, in ketamine's rapid antidepressant effects. Here, these findings are put into context and their significance is discussed.
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