Atomoxetine HCl is a potent and selective norepinephrine uptake inhibitor, with Ki values of 5, 77, and 1451nM for norepinephrine, serotonin (5-HT) and dopamine (DA) [1]. Atomoxetine HCl inhibits cloned human Ether-à-Go-Go-Related Gene (hERG) channels, with an IC50 value of 6.3µM[2]. Atomoxetine HCl can regulate the gene expression of neurotransmitter receptors and synaptic signaling molecules in fruit flies, and increase the locomotor activity of wild-type fruit flies[3]. Atomoxetine HCl has been widely used in animal models of Attention-Deficit/Hyperactivity Disorder (ADHD) to improve hyperactivity symptoms[4].
In vitro, Atomoxetine HCl treatment (50μM) for 7 days induced cell death in human neuron-like cells, resulting in a significant increase in mitochondrial ROS production[5]. Treatment with 50ng/ml Atomoxetine HCl for 24 hours significantly reduced the expression level of 8-hydroxyguanine glycosylase 1 (hOGG1) in U-937 cells[6]. In differentiated human SH-SY5Y neuroblastoma cells treated with 50μM Atomoxetine HCl for 7 days, the expressions of SDHA and COX-I were significantly downregulated, and mitochondrial fusion and mitochondrial division were disrupted[7].
In vivo, Atomoxetine HCl treatment for 10 days at a dose of 3mg/kg/day by intraperitoneal, intraperitoneal improved the spatial reference memory of adult rats, and enhanced the attention and inhibitory response control ability of adult rats[8]. Continuous intraperitoneal injection of Atomoxetine HCl (30mg/kg) once daily for 3 consecutive days can prevent ischemic neuronal death in the hippocampus of gerbils and significantly reduce the activation of glial cells caused by ischemia[9].
References:
[1] Bymaster F P, Katner J S, Nelson D L, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder[J]. Neuropsychopharmacology, 2002, 27(5): 699-711.
[2] Scherer D, Hassel D, Bloehs R, et al. Selective noradrenaline reuptake inhibitor atomoxetine directly blocks hERG currents[J]. British journal of pharmacology, 2009, 156(2): 226-236.
[3] Qu S, Zhou X, Wang Z, et al. The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment[J]. Molecular Psychiatry, 2024, 29(1): 165-185.
[4] Moon S J, Kim C J, Lee Y J, et al. Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD)[J]. PLoS One, 2014, 9(10): e108918.
[5] Corona J C, Carreón-Trujillo S, González-Pérez R, et al. Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells[J]. Scientific reports, 2019, 9(1): 13011.
[6] Schmidt A J, Clement H W, Gebhardt S, et al. Impact of psychostimulants and atomoxetine on the expression of 8-hydroxyguanine glycosylase 1 in human cells[J]. Journal of neural transmission, 2010, 117(6): 793-797.
[7] Carreón-Trujillo S, Vázquez-González D, Corona J C. Atomoxetine Decreases Mitochondrial Biogenesis, Fission and Fusion In Human Neuron-like Cells But Does Not Alter Antioxidant Defences[J]. Cell Biochemistry and Biophysics, 2023, 81(1): 105-115.
[8] Callahan P M, Plagenhoef M R, Blake D T, et al. Atomoxetine improves memory and other components of executive function in young-adult rats and aged rhesus monkeys[J]. Neuropharmacology, 2019, 155: 65-75.
[9] Park J H, Shin B N, Chen B H, et al. Neuroprotection and reduced gliosis by atomoxetine pretreatment in a gerbil model of transient cerebral ischemia[J]. Journal of the neurological sciences, 2015, 359(1-2): 373-380.
Atomoxetine HCl是一种强效、选择性的去甲肾上腺素摄取抑制剂，对去甲肾上腺素、血清素（5-HT）和多巴胺（DA）的Ki值分别为5、77和1451nM[1]。Atomoxetine HCl能抑制克隆的人Ether-à-Go-Go相关基因（hERG）通道，IC50值为6.3µM[2]。Atomoxetine HCl可调节果蝇体内神经递质受体和突触信号分子的基因表达，并增加野生型果蝇的运动活性[3]。Atomoxetine HCl已被广泛用于注意力缺陷/多动障碍（ADHD）的动物模型，以改善多动症状[4]。
在体外，使用50µM的Atomoxetine HCl处理7天，可诱导人神经元样细胞死亡，导致线粒体ROS生成显著增加[5]。使用50ng/ml的Atomoxetine HCl处理24小时，显著降低了U-937细胞中8-羟基鸟嘌呤糖苷酶1（hOGG1）的表达水平[6]。在使用50µM的Atomoxetine HCl处理7天的分化人SH-SY5Y神经母细胞瘤细胞中，SDHA和COX-I的表达显著下调，线粒体融合与分裂过程被破坏[7]。
在体内，每日腹腔注射3mg/kg剂量的Atomoxetine HCl，持续10天，改善了成年大鼠的空间参考记忆，并增强了注意力和抑制反应控制能力[8]。连续3天每日腹腔注射Atomoxetine HCl（30mg/kg），可预防沙土鼠海马中的缺血性神经元死亡，并显著减轻由缺血引起的胶质细胞活化[9]。