Ladostigil hydrochloride

Ladostigil (TV-3326) hydrochloride is an orally active dual inhibitor of cholinesterase and brain-selective monoamine oxidase (MAO), with IC50s of 37.1 and 31.8 μM for MAO-B and AChE, respectively. Ladostigil hydrochloride exhibits neuroprotective, antioxidant and anti-inflammatory activities. Ladostigil can be used for the research of depression and Alzheimer's disease[1][2].

Signaling Pathways >> Neuronal Signaling >> Monoamine Oxidase

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> AChE

AChE:31.8 μM (IC50)

MAO-B:37.1 μM (IC50)

Ladostigil (1-10 µM) hydrochloride 具有神经保护活性，包括防止线粒体膜电位 (ψ) 下降，衰减凋亡级联和抑制 OS 损伤诱导的 ROS 产生[2]。 Ladostigil (1-10 µM) hydrochloride 具有显著的神经保护活性，包括抑制 caspase-3 激活，诱导 Bcl-2，降低人成神经细胞瘤 SK-N-SH 细胞中 Bad 和 Bax 基因和蛋白的表达[2]。

Ladostigil (17 mg/kg; p.o. daily for 6 weeks) hydrochloride 在从青春期到产前压力大鼠的成年期的高架十字迷宫 (EPM) 和强迫游泳测试 (FST) 测试中，消除了他们的高度焦虑和抑郁样行为[4]。 Ladostigil (50 μmol/kg; single p.o.) hydrochloride 在大鼠物体识别测试中恢复丧失的情景记忆[3]。 Animal Model: Pathogen-free (SPF) Sprague-Dawley rats[4] Dosage: 17 mg/kg Administration: Oral (added to the drinking water) daily for 6 weeks Result: Inhibited brain MAO-A and B by more than 60%. Reduced hyperanxiety of male and female prenatally stressed (PS) rats in the EPM and depressive-like behaviour in the FST.

[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.