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1-(R)-氨基茚满,抗帕金森病药物雷沙吉兰的主要代谢产物的神经保护机制。

The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline.

机构信息

Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute, Technion-Faculty of Medicine, Haifa, Israel.

出版信息

J Neurochem. 2010 Mar;112(5):1131-7. doi: 10.1111/j.1471-4159.2009.06542.x. Epub 2009 Dec 10.

Abstract

The anti-parkinsonian drug, rasagiline [N-propargyl-1-(R)-aminoindan; Azilect(R)], is a secondary cyclic benzylamine and indane derivative, which provides irreversible, potent monoamine oxidase-B (MAO-B) inhibition and possesses neuroprotective and neurorestorative activities. A prospective clinical trial has shown that rasagiline confers significant symptomatic improvement and demonstrated alterations in Parkinson's disease progression. Rasagiline is primarily metabolized by hepatic cytochrome P-450 to form its major metabolite, 1-(R)-aminoindan, a non-amphetamine, weak reversible MAO-B inhibitor compound. Recent studies indicated the potential neuroprotective effect of 1-(R)-aminoindan, suggesting that it may contribute to the overall neuroprotective and antiapoptotic effects of its parent compound, rasagiline. This review article briefly highlights the molecular mechanisms underlying the neuroprotective properties of the active metabolite of rasagiline, 1-(R)-aminoindan, supporting the valuable potential of rasagiline for disease modification.

摘要

抗帕金森病药物雷沙吉兰[N-丙炔基-1-(R)-氨基茚满;Azilect®]是一种次级环状苄胺和茚满衍生物,可提供不可逆、强效单胺氧化酶-B(MAO-B)抑制作用,具有神经保护和神经修复作用。一项前瞻性临床试验表明,雷沙吉兰可显著改善症状,并改变帕金森病的进展。雷沙吉兰主要通过肝细胞色素 P-450 代谢形成其主要代谢物 1-(R)-氨基茚满,这是非安非他命、弱可逆 MAO-B 抑制剂化合物。最近的研究表明,1-(R)-氨基茚满具有潜在的神经保护作用,表明它可能有助于其母体化合物雷沙吉兰的整体神经保护和抗细胞凋亡作用。本文简要概述了雷沙吉兰活性代谢物 1-(R)-氨基茚满的神经保护特性的分子机制,支持雷沙吉兰在疾病修饰方面的潜在价值。

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