Rasagiline - a novel MAO B inhibitor in Parkinson's disease therapy

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative, dopamine deficiency disorder. The main therapeutic strategies for PD treatment relies on dopamine precursors (levodopa), inhibition of dopamine metabolism (monoamine oxidase [MAO] B and catechol-O-methyl transferase inhibitors), and dopamine receptor agonists. Recently, a novel selective and irreversible MAO B propargylamine inhibitor rasagiline (N-propargyl-1-R-aminoindan, Azilect((R))) was approved for PD therapy. In contrast to selegiline, the prototype of MAO B inhibitors, rasagiline is not metabolized to potentially toxic amphetamine metabolites. The oral bioavailability of rasagiline is 35%, it reaches T(max) after 0.5-1 hours and its half-life is 1.5-3.5 hours. Rasagiline undergoes extensive hepatic metabolism primarily by cytochrome P450 type 1A2 (CYP1A2). Rasagiline is initiated at 1 mg once-daily dosage as monotherapy in early PD patients and at 0.5-1 mg once-daily as adjunctive to levodopa in advanced PD patients. Rasagiline treatment was not associated with "cheese effect" and up to 20 mg per day was well tolerated. In PD patients with hepatic impairment, rasagiline dosage should be carefully adjusted. Rasagiline should not be administered with other MAO inhibitors and co-administration with certain antidepressants and opioids should be avoided. Although further clinical evidence is needed on the neuroprotective effects of rasagiline in PD patients, this drug provides an additional tool for PD therapy.

Keywords: MAO B inhibition; neuroprotection; rasagiline; safety; therapy.

Figure 1

Schematic of the major dopaminergic therapeutic strategies for Parkinson’s treatment. Step 1, dopamine precursor L-dopa; Step 2, dopamine receptor agonists; Step 3, dopamine metabolizing enzymes (COMT and MAO B) inhibitors; Step 4, neuroprotective compounds. +, increase in the synaptic dopamine or stimulation of dopamine receptors and survival pathways; −, inhibition of dopamine metabolizing enzymes or apoptotic pathways; ▲, dopamine neurotransmitter;V, dopamine receptors; DA, dopamine; MAO B, monoamine oxidase type B; COMT, cathechol-O-methyl transferase.