Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity.
Rasagiline (N-propargyl-1-(R)-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO)-B inhibitor, anti-Parkinsonian drug. Rasagiline is effective as monotherapy or adjunct to L-Dopa for patients with early and late Parkinson's disease (PD). Its S-isomer, TVP1022 is thousand times less potent as an MAO-B inhibitor. However, both compounds have similar molecular mechanisms of neuroprotection in neuronal cell cultures and animal neurodegenerative models, indicating that the neuroprotective effect of rasagiline does not depend on inhibition of MAO-B, but rather is associated with the N-propargyl moiety, which promotes mitochondrial viability and stabilizes permeability transition by regulating Bcl-2 family proteins. Novel findings demonstrated that the major metabolite of rasagiline, 1-(R)-aminoindan has antioxidant and neuroprotective capabilities and thus, may contribute to the overt activity of its parent compound, rasagiline. This paper will review the earlier and present studies in the development of rasagiline for treatment of PD and discuss its pharmacology and applicable mechanism of action.
Weinreb
Orly
O
Eve Topf Centre of Excellence for Neurodegenerative Diseases, Technion-Rappaport Faculty of Medicine, Efron St. PO Box 9697, Haifa 31096, Israel.
Amit
Tamar
T
Bar-Am
Orit
O
Youdim
Moussa B H
MB
D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D009414:Nerve Growth Factors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D020836:Protein Structure, Quaternary; D012642:Selegiline / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D000978:Antiparkinson Agents; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C031967:rasagiline; D012642:Selegiline; D008995:Monoamine Oxidase