Rasagiline Mesylate, a New Mao-B Inhibitor for the Treatment of Parkinson's Disease: A Double-Blind Study as Adjunctive Therapy to Levodopa

Abstract

Rasagiline mesylate (TVP-1012) is a potent, selective, non-reversible MAO-B inhibitor, without the tyramine-potentiating effect and with neuroprotective activities. The benefit of rasagiline as monotherapy in patients with early Parkinson's disease (PD) has already been reported. To evaluate the safety, tolerability, and clinical effect of rasagiline as adjunctive therapy to levodopa, a multicenter, double-blind, randomized, placebo-controlled, parallel-group study (0.5, 1, and 2 mg/d) was conducted for 12 weeks in 70 patients with PD (mean age, 57.4 y; mean disease duration, 5.7 y; 32 patients had motor fluctuations). A beneficial clinical effect was observed in fluctuating patients treated with rasagiline (all doses), expressed as a decrease in total Unified Parkinson's Disease Rating Scale (UPDRS) score (23.0% vs 8.5% in the placebo group). The treatment effect was still evident 6 weeks after drug discontinuation (in all doses). The safety and tolerability of rasagiline were good. Adverse events were no different than those of patients taking placebo. Almost complete platelet MAO-B inhibition was obtained at all rasagiline doses. This study has demonstrated that rasagiline (up to 2 mg/day) has a good safety profile and a beneficial clinical effect in fluctuating patients with PD when given as an add-on to chronic levodopa therapy.

Driving GDNF expression: The green and the red traffic lights

“…Therefore, the effect of selegiline on GDNF expression seems to be independent of its effect on MAO activity but is not clear whether it involves the enhancement of the impulse mediated release of catecholamines, the so called ''catecholaminergic activity enhancement'' (CAE; Knoll, 1998). Another MAO-B inhibitor, rasagiline (N-propargyl-(1R)-aminoindan), is used as monotherapy in PD and as adjunctive therapy for patients receiving L-DOPA (Rabey et al, 2000;Parkinson Study Group, 2002a). Rasagiline may slow the rate of progression of PD (Siderowf and Stern, 2006) and displays neuroprotective activity in in vivo models of neurodegenerative diseases (reviewed by Youdim et al, 2005).…”

A role of the MAO-B inhibitor rasagiline in treatment of Parkinson’s disease

“…По химической структуре он представляет собой N-пропаргил-1-(R)-аминоиндан. Хотя разагилин имеет тот же механизм действия, что и селегилин, при его мета-болизме не образуется метамфетамин, с которым связана значительная часть побочных эффектов селегилина [3,10]. Более того, основной метаболит разагилина -амино-индан -улучшает двигательные и когнитивные функции в экспериментальных моделях и может таким образом усиливать эффект основного препарата.…”

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“…7 In comparison to selegiline, rasagiline has the benefit of being metabolised to 1-Raminoindan rather than the potentially neurotoxic methamphetamine. 8 Aminoindan has also demonstrated favourable pharmacological activity in experimental models relevant to PD. 8 Rasagiline is well absorbed and readily crosses the blood-brain barrier.…”

“…8 Aminoindan has also demonstrated favourable pharmacological activity in experimental models relevant to PD. 8 Rasagiline is well absorbed and readily crosses the blood-brain barrier.…”