Eve Topf Center of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Technion-Faculty of Medicine, Rappaport Family Research Institute, Haifa, Israel.
Antioxid Redox Signal. 2011 Mar 1;14(5):767-75. doi: 10.1089/ars.2010.3282. Epub 2010 Dec 28.
The anti-Parkinsonian, monoamine oxidase-B inhibitor drug, rasagiline (Azilect®), is primarily metabolized by hepatic cytochrome P450 isoenzyme 1A2-mediated N-dealkylation to form its major metabolite, 1-(R)-aminoindan. The present study was undertaken to further investigate, for the first time, the possible neuroprotective effect of 1-(R)-aminoindan in two rat models of Parkinson's disease, the 6-hydroxydopamine- and lactacystin (a proteasomal inhibitor)-induced nigrostriatal degeneration. 1-(R)-aminoindan reversed behavioral asymmetry and restored striatal catecholamine levels in these two rat models and significantly protected neurons from hydrogen peroxide-induced oxidative stress. These observations indicate that 1-(R)-aminoindan may contribute to the overall neuroprotective activity of its parental compound, rasagiline.
抗帕金森病、单胺氧化酶-B 抑制剂药物雷沙吉兰(Azilect®)主要通过肝细胞色素 P450 同工酶 1A2 介导的 N-去烷基化代谢生成其主要代谢物 1-(R)-氨基茚满。本研究首次进一步探讨了 1-(R)-氨基茚满在两种帕金森病大鼠模型中的可能神经保护作用,即 6-羟多巴胺和乳清酸(蛋白酶体抑制剂)诱导的黑质纹状体变性。1-(R)-氨基茚满逆转了这两种大鼠模型中的行为不对称,并恢复了纹状体儿茶酚胺水平,并且显著保护神经元免受过氧化氢诱导的氧化应激。这些观察结果表明,1-(R)-氨基茚满可能有助于其母体化合物雷沙吉兰的整体神经保护活性。