[olsen]

Neurochem Res. 2007 Aug 16; [Epub ahead of print] Links
Rasagiline Promotes Regeneration of Substantia Nigra Dopaminergic Neurons in Post-MPTP-induced Parkinsonism via Activation of Tyrosine Kinase Receptor Signaling Pathway.
Mandel SA, Sagi Y, Amit T.
Eve Topf Center of Excellence for Neurodegenerative Diseases Research, Department of Pharmacology, Technion-Rappaport Faculty of Medicine, P.O. Box 9697, Haifa, 31096, Israel, mandel@tx.tchnion.ac.il.

The anti-Parkinson drug rasagiline (Azilect), an irreversible and selective monoamine oxidase (MAO)-B inhibitor, was shown to possess neuroprotective activities, involving multiple survival pathways among them the up-regulation of protein kinase C (PKC)alpha, PKCepsilon, the anti-apoptotic Bcl-2, Bcl-xL, and Bcl-w and the induction of brain-derived- and glial cell line-derived neurotrophic factors (BDNF, GDNF). More recently, employing conventional neurochemical techniques, as well as transcriptomic and proteomic screening tools, combined with a biology-based clustering method, it was shown that rasagiline also possesses neurorescue/neurogenesis activity in mice midbrain dopaminergic neurons when given chronically, post-MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). This action was attributed to the activation of cell signaling mediators associated with neurotrophic factors responsive-tyrosine kinase receptor (Trk) pathway, including ShcC, SOS, AF6, Rin1, and Ras and the increase in the Trk-downstream effecter phosphatidylinositol 3 kinase (PI3K) protein and its substrate, Akt/PKB. It is interesting to determine whether a similar effect is seen in Parkinsonian patients after long-term treatment with rasagiline, which may have implications as a possible disease modifying agent.

PMID: 17701352 [PubMed - as supplied by publisher

[olsen]

Drugs. 2007;67(12):1725-47.
Rasagiline: a review of its use in the management of Parkinson's disease.
Oldfield V, Keating GM, Perry CM.

Wolters Kluwer Health | Adis, Auckland, New Zealand, an editorial office of Wolters Kluwer Health, Conshohocken, Pennsylvania, USA.

Rasagiline (Azilect((R))) is a novel, selective, irreversible second-generation inhibitor of monoamine oxidase type B (MAO-B). It is administered orally once daily and is approved in the US, Canada, Mexico, Israel and the EU for use as monotherapy and as adjunct therapy in the treatment of Parkinson's disease.Results of well designed clinical studies indicate that rasagiline is effective as initial monotherapy and improves Parkinson's symptomatology in patients with early Parkinson's disease. In addition, when administered in conjunction with levodopa, in patients with moderate to advanced disease and motor fluctuations, rasagiline reduces mean daily 'off' time and increases daily 'on' time without troublesome dyskinesias, compared with controls. Rasagiline is generally well tolerated as monotherapy and adjunctive therapy and is administered once daily. Thus, rasagiline, administered as a simple and convenient dosage regimen, is a well tolerated and effective option for monotherapy in patients with early Parkinson's disease and for adjunctive therapy in patients with moderate to advanced disease.

PMID: 17683172 [PubMed - in process]