a Department of Drug Discovery and Development , Harrison School of Pharmacy, Auburn University , Auburn , AL , USA.
b Department of Pharmacology, Faculty of Medicine , Jeddah University , Jeddah , KSA.
Toxicol Mech Methods. 2018 Mar;28(3):177-186. doi: 10.1080/15376516.2017.1376024. Epub 2017 Sep 28.
Benzylpiperazine has been designated as Schedule I substance under the Controlled Substances Act by Drug Enforcement Administration. Benzylpiperazine is a piperazine derivative, elevates both dopamine and serotonin extracellular levels producing stimulatory and hallucinogenic effects, respectively, similar to methylenedioxymethamphetamine (MDMA). However, the comparative neurotoxic effects of Piperazine derivatives (benzylpiperazine and benzoylpiperazine) have not been elucidated. Here, piperazine derivatives (benzylpiperazine and benzoylpiperazine) were synthesized in our lab and the mechanisms of cellular-based neurotoxicity were elucidated in a dopaminergic human neuroblastoma cell line (SH-SY5Y). We evaluated the in vitro effects of benzylpiperazine and benzoylpiperazine on the generation of reactive oxygen species, lipid peroxidation, mitochondrial complex-I activity, catalase activity, superoxide dismutase activity, glutathione content, Bax, caspase-3, Bcl-2 and tyrosine hydroxylase expression. Benzylpiperazine and benzoylpiperazine induced oxidative stress, inhibited mitochondrial functions and stimulated apoptosis. This study provides a germinal assessment of the neurotoxic mechanisms induced by piperazine derivatives that lead to neuronal cell death.
苯甲哌嗪已被美国缉毒局指定为《管制物质法》下的附表 I 物质。苯甲哌嗪是一种哌嗪衍生物，分别升高多巴胺和血清素的细胞外水平，产生兴奋和致幻作用，类似于亚甲二氧基甲基苯丙胺（MDMA）。然而，哌嗪衍生物（苯甲哌嗪和苯甲酰哌嗪）的比较神经毒性作用尚未阐明。在这里，哌嗪衍生物（苯甲哌嗪和苯甲酰哌嗪）在我们的实验室中合成，并在多巴胺能人神经母细胞瘤细胞系（SH-SY5Y）中阐明了基于细胞的神经毒性的机制。我们评估了苯甲哌嗪和苯甲酰哌嗪对活性氧生成、脂质过氧化、线粒体复合物-I 活性、过氧化氢酶活性、超氧化物歧化酶活性、谷胱甘肽含量、Bax、caspase-3、Bcl-2 和酪氨酸羟化酶表达的体外影响。苯甲哌嗪和苯甲酰哌嗪诱导氧化应激、抑制线粒体功能并刺激细胞凋亡。这项研究对导致神经元细胞死亡的哌嗪衍生物引起的神经毒性机制进行了初步评估。
