The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline.
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.
Bar-Am
Orit
O
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.
Weinreb
Orly
O
Amit
Tamar
T
Youdim
Moussa B H
MB
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007189:Indans / Q000378:metabolism* / Q000627:therapeutic use*; D008956:Models, Chemical; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism
D007189:Indans; D018696:Neuroprotective Agents; D051560:Proto-Oncogene Proteins c-bcl-6; C031967:rasagiline; C006545:2-aminoindan; D003577:Cytochrome P-450 Enzyme System