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

被引:58
作者
Bar-Am, Orit
Weinreb, Orly
Amit, Tamar
Youdim, Moussa B. H. [1 ]
机构
[1] Technion Israel Inst Technol, Fac Med, Dept Pharmacol, Rappaport Family Res Inst, IL-31096 Haifa, Israel
关键词
1-(R)-aminoindan; antiapoptotic; Bcl-2 family proteins; neuroprotection; Parkinson's disease; rasagiline; PROTEIN-KINASE-C; OXIDASE-B INHIBITOR; MONOAMINE-OXIDASE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; BCL-2; FAMILY; ENDOGENOUS NEUROTOXIN; DELAYED-START; SH-SY5Y CELLS; DOUBLE-BLIND; CHOLINESTERASE;
D O I
10.1111/j.1471-4159.2009.06542.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
P>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.
引用
收藏
页码:1131 / 1137
页数:7
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