Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent, irreversible
monoamine oxidase (
MAO)-B inhibitor designed for use as an antiparkinsonian
drug. Unlike
selegiline,
rasagiline is not derived from
amphetamine or metabolized to neurotoxic l-
methamphetamine derivative, and it does not have
sympathomimetic activity. Moreover, at selective
MAO-B inhibitory dosage, it does not induce a "cheese reaction."
Rasagiline is effective as monotherapy or as an adjunct to
L-dopa for patients with early and late
Parkinson's disease. Adverse events do not occur with greater frequency in subjects receiving
rasagiline than in those on placebo. Its S-isomer,
TVP1022, is more than a thousand times less potent as an
MAO inhibitor. However, both drugs have neuroprotective activities in neuronal cell cultures in response to various
neurotoxins, as well as in vivo (e.g., in response to global
ischemia, neurotrauma,
head injury,
anoxia, etc.), indicating that
MAO inhibition is not a prerequisite for neuroprotection. The neuroprotective activity of these drugs has been demonstrated to be associated with the
propargylamine moiety, which protects mitochondrial viability and
mitochondrial permeability transition pore by activating Bcl-2 and downregulating the Bax family of
proteins.
Rasagiline processes
amyloid precursor
protein (APP) into the neuroprotective-neurotrophic soluble APPalpha (sAPPalpha) by
protein kinase C- and
mitogen-activated protein kinase-dependent activation of
alpha-secretase, and increases
nerve growth factor,
glial cell- derived neurotrophic factor (
GDNF) and
brain-derived neurotrophic factor (
BDNF) expression and
proteins. Thus,
rasagiline may induce neuroprotection, neuroplasticity and long-term potentiation.
Rasagiline has therefore been chosen by the National Institutes of Health (NIH) to study its
neuroprotective effects in
neurodegenerative diseases. Long-term studies are required to evaluate the
drug's disease-modifying prospects in Parkinson's and
Alzheimer's diseases.