Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Block 23, Sofia,, 1113, Bulgaria.
Department of Chemistry, South-West University "Neofit Rilski", Ivan Mihailov St. 66, Blagoevgrad,, 2700, Bulgaria.
J Mol Neurosci. 2022 Apr;72(4):900-909. doi: 10.1007/s12031-021-01964-x. Epub 2022 Jan 28.
The neuroprotective capacity of newly synthesized amantadine derivative tyrosinyl-amantadine (Tyr-Am) with expected antiparkinsonian properties was evaluated in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Male Wistar rats were divided into the following groups: sham-operated (SO), striatal 6-OHDA-lesioned control group, 6-OHDA-lesioned rats pretreated for 6 days with Tyr-Am (16 mg/kg administered intraperitoneally, i.p.), and 6-OHDA-lesioned rats pretreated for 6 days with amantadine (40 mg/kg i.p.), used as a referent. On the first, second and third week post-lesion, the animals were subjected to some behavioral tests (apomorphine-induced rotation, rotarod, and passive avoidance test). The acetylcholinesterase (AChE) activity and key oxidative stress parameters including lipid peroxidation levels (LPO) and superoxide dismutase (SOD) were measured in brain homogenates. The results showed that the neuroprotective effect of Tyr-Am was comparable to that of amantadine, improving neuromuscular coordination and learning and memory performance even at a 2.5-fold lower dose. Tyr-Am demonstrated significant antioxidant properties via decreased LPO levels but had no effect on AChE activity. We can conclude that the newly synthesized amantadine derivative Tyr-Am demonstrated significant antiparkinsonian activity in a 6-OHDA experimental model.
新合成的具有抗帕金森病特性的金刚烷衍生物酪氨酸-金刚烷（Tyr-Am）的神经保护能力在 6-羟多巴胺（6-OHDA）帕金森病模型中进行了评估。雄性 Wistar 大鼠分为以下几组：假手术（SO）组、纹状体 6-OHDA 损伤对照组、6-OHDA 损伤大鼠用 Tyr-Am（16 mg/kg 腹腔注射，i.p.）预处理 6 天组和 6-OHDA 损伤大鼠用金刚烷（40 mg/kg i.p.）预处理 6 天组，用作参照。在损伤后第 1、2 和第 3 周，动物进行了一些行为测试（阿扑吗啡诱导旋转、旋转棒和被动回避测试）。在脑匀浆中测量乙酰胆碱酯酶（AChE）活性和关键氧化应激参数，包括脂质过氧化水平（LPO）和超氧化物歧化酶（SOD）。结果表明，Tyr-Am 的神经保护作用可与金刚烷相媲美，即使剂量低 2.5 倍，也能改善神经肌肉协调性和学习记忆能力。Tyr-Am 通过降低 LPO 水平表现出显著的抗氧化特性，但对 AChE 活性没有影响。我们可以得出结论，新合成的金刚烷衍生物 Tyr-Am 在 6-OHDA 实验模型中表现出显著的抗帕金森病活性。
