Norfluoxetine (hydrochloride) is an active metabolite of fluoxetine produced in the liver via N-demethylation and has oral activity[1]. Norfluoxetine (hydrochloride) is mainly used in research on diseases such as depression, obsessive-compulsive disorder, bipolar disorder, epilepsy, and bulimia nervosa[2-3].
In vitro, Norfluoxetine (hydrochloride) (0.03-30µM) treatment of MCF-7 cells for 72 hours significantly inhibited cell proliferation at 15-30µM[4]. Norfluoxetine (hydrochloride) (10µM) treatment of primary microglia for 24-72 hours reduced protein levels in cell lysates, decreased cell viability, and increased the expression of caspase-3, an apoptosis marker, in microglia[5]. Norfluoxetine (hydrochloride) (0.01-20µM) treatment of estrogen receptor-positive T47D-KBluc human breast cancer cells for 24 hours significantly reduced cell viability at 15-20µM[6].
In vivo, Norfluoxetine (hydrochloride) (1, 5, and 10mg/kg; 12h; i.p.) in male C57BL/6 mice treated with MPTP (20mg/kg) inhibited MPTP-induced degeneration of dopamine neurons in the substantia nigra, protected DA neurons from MPTP neurotoxicity, and inhibited microglial activation and NADPH oxidase-derived oxidative stress in cells[7].
References:
[1]. Heikkinen T, Ekblad U, Palo P, et al. Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation[J]. Clinical Pharmacology & Therapeutics, 2003, 73(4): 330-337.
[2]. Amsterdam J D, Fawcett J, Quitkin F M, et al. Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study[J]. American Journal of Psychiatry, 1997, 154(7): 963-969.
[3]. Kecskeméti V, Rusznák Z, Riba P, et al. Norfluoxetine and fluoxetine have similar anticonvulsant and Ca2+ channel blocking potencies[J]. Brain research bulletin, 2005, 67(1-2): 126-132.
[4]. Lupu D, Pop A, FIZEȘAN I, et al. In vitro effects of fluoxetine and norfluoxetine on breast cancer proliferation[J]. Far macia, 2017, 4: 532-536.
[5]. Dhami K S, Churchward M A, Baker G B, et al. Fluoxetine and its metabolite norfluoxetine induce microglial apoptosis[J]. Journal of Neurochemistry, 2019, 148(6): 761-778.
[6]. Lupu D, Pop A, Cherfan J, et al. In vitro modulation of estrogen receptor activity by norfluoxetine[J]. Clujul Medical, 2015, 88(3): 386.
[7]. Kim K I, Chung Y C, Jin B K. Norfluoxetine Prevents Degeneration of Dopamine Neurons by Inhibiting Microglia‐Derived Oxidative Stress in an MPTP Mouse Model of Parkinson’s Disease[J]. Mediators of inflammation, 2018, 2018(1): 4591289.
Norfluoxetine (hydrochloride)是Fluoxetine在肝脏中通过N-去甲基化产生的活性代谢物，具有口服活性[1]。Norfluoxetine (hydrochloride)主要应用于抑郁症、强迫症、双相情感障碍、癫痫及神经性贪食症等疾病的相关研究[2-3]。
在体外，Norfluoxetine (hydrochloride)（0.03-30µM）处理MCF-7细胞72小时，在15-30µM时显著抑制了细胞增殖[4]。Norfluoxetine (hydrochloride)（10µM）处理原发性小胶质细胞24-72小时，降低了细胞裂解物中的蛋白质水平，降低了细胞存活率，并提高了小胶质细胞中凋亡标志物切割半胱天冬酶3的表达[5]。Norfluoxetine (hydrochloride)（0.01-20µM）处理雌激素受体阳性T47D-KBluc人类乳腺癌细胞24小时，在15-20µM时显著降低细胞存活率[6]。
在体内，Norfluoxetine (hydrochloride)（1, 5, and 10mg/kg; 12h; i.p.）在MPTP（20mg/kg）处理后治疗雄性C57BL/6小鼠，能够抑制因MPTP导致的小鼠黑质中多巴胺神经元的退化，保护DA神经元免受MPTP的神经毒性，抑制小胶质细胞活化以及细胞中NADPH氧化酶衍生的氧化应激[7]。