| 描述 |
Ladostigil (TV-3326) 是胆碱酯酶 (cholinesterase) 和脑选择性单胺氧化酶 (MAO) 的双重抑制剂,抑制 MAO-B 和 AChE 的 IC50 值分别为 37.1 和 31.8 μM。Ladostigil 能够增加胆碱能的传递,防止 ROS 的形成或其作用,可用于抑郁症和阿尔茨海默氏病的研究。
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| 相关类别 |
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| 靶点 |
MAO-B:37.1 μM (IC50)
AChE:31.8 μM (IC50)
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| 体外研究 |
Ladostigil(1-10µM)具有神经保护作用,包括防止线粒体膜电位(ψ)下降、减少凋亡级联和抑制OS损伤诱导的ROS生成[2]。Ladostigil(1-10µM)具有显著的神经保护活性,包括抑制caspase-3激活,诱导Bcl-2,减少Bad和Bax基因及蛋白在人神经母细胞瘤SK-N-SH细胞中的表达[2]。
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| 体内研究 |
Ladostigil(17 mg/kg；每天一次,持续6周)可以消除从青春期到出生前应激大鼠在高架迷宫(EPM)和强迫游泳试验(FST)中的过度紧张和抑郁样行为[4]。拉多西地尔(50μmol/kg；单次给药)可恢复大鼠在物体识别实验中的情景记忆丧失[3]。动物模型：无病原体(SPF)Sprague-Dawley大鼠[4]剂量：17mg/kg给药：P.o.(添加到饮用水中)连续6周。结果：脑MAO-A和MAO-B抑制率超过60%。EPM中雄性和雌性产前应激(PS)大鼠的过度紧张和FST中抑郁样行为的降低。
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| 参考文献 |
[1]. Denya I, et, al. Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer's disease. Medchemcomm. 2018 Jan 16; 9(2):357-370. [2]. Weinreb O, et, al. Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr Drug Targets. 2012 Apr; 13(4): 483-94. [3]. Weinstock M, et, al. Ladostigil, a novel multifunctional drug for the treatment of dementia co-morbid with depression. J Neural Transm Suppl. 2006; (70):443-6. [4]. Poltyrev T, et, al. Effect of chronic treatment with ladostigil (TV-3326) on anxiogenic and depressive-like behaviour and on activity of the hypothalamic-pituitary-adrenal axis in male and female prenatally stressed rats. Psychopharmacology (Berl). 2005 Aug;181(1): 118-25.
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CAS号209394-46-7
