氯胺酮
NMDA受体
抗抑郁药
药理学
突触可塑性
神经可塑性
PI3K/AKT/mTOR通路
神经营养因子
神经科学
心理学
医学
信号转导
化学
海马体
受体
内科学
生物化学
作者
Ellen Scotton,Bárbara Antqueviezc,Mailton Vasconcelos,Giovana Dalpiaz,Luíza Paul Géa,Jéferson Ferraz Goularte,Rafael Colombo,Adriane Ribeiro Rosa
标识
DOI:10.1016/j.bcp.2022.114963
摘要
Approximately one-third of individuals with major depressive disorder are resistant to conventional antidepressants (i.e., monoamine-based therapies), and, even among respondents, a proper therapeutic effect may require weeks of treatment. Ketamine, a racemic mixture of the two enantiomers, (R)-ketamine and (S)-ketamine, is an N-methyl-d-aspartate receptor (NMDAR) antagonist and has been shown to have rapid-acting antidepressant properties in patients with treatment-resistant depression (TRD). Although (R)-ketamine has a lower affinity for NMDAR, it presents greater potency and longer-lasting antidepressant properties, with no major side effects, than racemic ketamine or (S)-ketamine in preclinical findings. Thereby, ketamine and its enantiomers have not only an antagonistic effect on NMDAR but also a strong synaptogenic-modulatory effect, which is impaired in TRD pathophysiology. In this review, we summarize the current evidence regarding the modulation of neurotransmission, neuroplasticity, and neural network activity as putative mechanisms of these rapid-acting antidepressants, highlighting differences on intracellular signaling pathways of synaptic proteins such as mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK) and brain-derived neurotrophic factor (BDNF). In addition, we discuss probable mechanisms involved in the side effects of ketamine and its enantiomers.
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