生物活性

• 描述Fluoxetine is the first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. Fluoxetine blocks the downregulation of cell proliferation resulting from inescapable shock (IS) of hippocampal cell. Fluoxetine treatment also reverses the deficit in escape latency observed in animals exposed to inescapable shock in adult male Sprague-Dawley rats^[3].Fluoxetine increases the number of newborn cells in the dentate gyrus of the hippocampus of adult rat. Fluoxetine also increases the number of proliferating cells in the prelimbic cortex. Fluoxetine (5 mg/kg) alone increases cell proliferation in the dentate gyrus. Coadministration (fluoxetine 5 mg/kg + olanzapine) also significantly increases the number of BrdU-positive cells compared with the control group^[4].Fluoxetine accelerates the maturation of immature neurons. Fluoxetine enhances neurogenesis-dependent long-term potentiation (LTP) in the dentate gyrus^[5].Fluoxetine, but not citalopram, fluvoxamine, paroxetine and sertraline, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Fluoxetine produces robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration^[6].Fluoxetine combined with Olanzapine produces robust, sustained increases of extracellular levels of dopamine ([DA](ex)) and norepinephrine ([NE](ex)) up to 361% and 272% of the baseline, respectively, which are significantly greater than either drug alone^[7].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02473250	Bipolar Disorder	Phase 4	Recruiting	September 2019	United States, New York ... more >> New York State Psychiatric Institute/Columbia University Medical Center Recruiting New York, New York, United States, 10032 Contact: Martin Lan, MD PHD    646-774-7610    martin.lan@NYSPI.COLUMBIA.EDU Collapse <<
  NCT00451490	Depressive Disorder, Major	Not Applicable	Withdrawn(This study not get t... more >>he approval by the drug company) Collapse <<	December 2007	Taiwan ... more >> National Taiwan University Hospital Taipei, Taiwan, 100 Collapse <<
  NCT01488266	Major Depressive Disorder	Not Applicable	Unknown	March 2013	Korea, Republic of ... more >> Korean Univ Ansan Hospital; Bucheon St.Mary Hospital; DonggukUniv Gyeongju Hospital; Catholic University of Korea St. Paul's Hospital Seoul, Korea, Republic of Taiwan Chang Gung Memorial Hospital; Kaohsiung Medical University Chung-ho Memorial Hospital Taipei, Taiwan Collapse <<

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• 参考文献

• [1] Wang JW, David DJ, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008 Feb 6;28(6):1374-84.

  [2] Malberg JE, Duman RS. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003 Sep;28(9):1562-71.

  [3] Malberg JE, et al. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 2003 Sep;28(9):1562-71.

  [4] Kodama M, et al. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry. 2004 Oct 15;56(8):570-80.

  [5] Wang JW, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008 Feb 6;28(6):1374-84.

  [6] Bymaster FP, et al. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl). 2002 Apr;160(4):353-61.

  [7] Zhang W, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology. 2000 Sep;23(3):250-62.

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