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.

Research highlights▶ A potent selective irreversible monoamine oxidase -B inhibitor/anti-Parkinson's drug. ▶ Neuroprotective and neurorestorative activities in vitro and in vivo. ▶ Maintenance of the mitochondria integrity and related proteins and enzymes. ▶ Induction of neurotrophic factors. ▶ Its major metabolite has neuroprotective effects by itself in vitro and in vivo.