(2R,6R)-Hydroxynorketamine promotes dendrite outgrowth in human inducible pluripotent stem cell-derived neurons through AMPA receptor with timing and exposure compatible with ketamine infusion pharmacokinetics in humans
作者: Ginetta ColloLaura CavalleriCristiano ChiamuleraEmilio Merlo Pich
作者单位: 1Department of Molecular and Translational Medicine, University of Brescia, Brescia
2Department of Diagnostics and Public Health, University of Verona, Verona, Italy
3Takeda Pharmaceuticals International AG, Zurich, Switzerland
刊名: NeuroReport, 2018
来源数据库: Wolters Kluwer Journal
DOI: 10.1097/WNR.0000000000001131
原始语种摘要: The mechanisms underlying the prolonged antidepressant effects after a single infusion of ketamine are only partially understood. Ketamine’s half-life of ∼2 h cannot explain antidepressant effects that last for 1 week, suggesting the triggering of long-lasting neuroplasticity. Recent human pharmacokinetics (PK) data indicate that a ketamine metabolite, (2R,6R)-hydroxynorketamine (HNK), persists in the high submicromolar range for additional 6–12 h. As in rodents HNK can induce dendrite outgrowth through AMPA receptor-mediated mechanisms, in this work, we aimed to show that HNK produces similar effects in human neurons at concentrations and exposure time compatible with human PK after ketamine infusion. Human dopaminergic neurons were differentiated in-vitro from inducible pluripotent stem...
全文获取路径: Wolters Kluwer 
影响因子:1.404 (2012)

  • ketamine 氯胺酮
  • pluripotent 多能的
  • outgrowth 成果
  • exposure 暴露
  • infusion 浸剂
  • receptor 接受体
  • human 人的
  • antidepressant 抗抑郁药
  • dendrite 师石
  • pretreatment 预处理