Pharmacology of Rasagiline, a New MAO-B Inhibitor Drug for the Treatment of Parkinson's Disease with Neuroprotective Potential.

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Finberg JP

Pharmacology of Rasagiline, a New MAO-B Inhibitor Drug for the Treatment of Parkinson's Disease with Neuroprotective Potential.

Rambam Maimonides Med J. 2010 Jul 2;1(1):e0003. doi: 10.5041/RMMJ.10003. Print 2010 Jul.

PubMed ID

23908775 [ View in PubMed

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Abstract

Rasagiline (Azilect) is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO) type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitrogen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine. Metabolic conversion of the compound in vivo is by hepatic cytochrome P450-1A2, with generation of 1-aminoindan as the major metabolite. Rasagiline possesses no amphetamine-like properties, by contrast with the related compound selegiline (Deprenyl, Jumex, Eldepryl). Although the exact distribution of MAO isoforms in different neurons and tissues is not known, dopamine behaves largely as a MAO-A substrate in vivo, but following loss of dopaminergic axonal varicosities from the striatum, metabolism by glial MAO-B becomes increasingly important. Following subchronic administration to normal rats, rasagiline increases levels of dopamine in striatal microdialysate, possibly by the build-up of beta-phenylethylamine, which is an excellent substrate for MAO-B, and is an effective inhibitor of the plasma membrane dopamine transporter (DAT). Both of these mechanisms may participate in the anti-Parkinsonian effect of rasagiline in humans. Rasagiline possesses neuroprotective properties in a variety of primary neuronal preparations and neuron-like cell lines, which is not due to MAO inhibition. Recent clinical studies have also demonstrated possible neuroprotective properties of the drug in human Parkinsonian patients, as shown by a reduced rate of decline of symptoms over time.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
(R)-N-methyl-N-2-propynyl-1-indanamine	Amine oxidase [flavin-containing] B	Protein	Humans	Unknown	Not Available	Details