Rasagiline – a novel MAO B inhibitor in Parkinson’s disease therapy

Figures & data

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.

Table 1 Clinical trials to evaluate rasagiline efficacy, safety, and side-effects

Study	Design	Treatment	Results	Conclusions	References
Double-blind study of rasagiline adjunctive to L-dopa therapy	Phase II, 12 weeks; 70 PD patients with advanced PD on L-dopa therapy	Doses: 0.5 mg, 1 mg, 2 mg, or placebo	No differences in incidence of side-effects. No significant changes in blood pressure and heart rate in any group. Despite good clinical response, no statistical difference in UPDRS scores between the drug and placebo groups	Rasagiline is well tolerated	Rabey et al 2000
Double-blind, randomized, trial of rasagiline as monotherapy in early PD	Phase II, 10 weeks; 56 early stage, untreated PD patients	Doses: 1 mg, 2 mg, 4 mg, or placebo	No differences in incidence of side effects between the drug and placebo groups. 10% mean improvement in UPDRS scores in rasagiline 2 mg group vs 2.8% improvement in the placebo group (p < 0.05)	Rasagiline is well tolerated and effective	Stern et al 2004
TEMPO - double-blind, randomized, placebo-controlled clinical trial of rasagiline as monotherapy in early PD	26 weeks; 404 untreated patients with early PD	Doses: 1 mg, 2 mg, or placebo	UPDRS improvement: 4.2 units (1 mg vs placebo), 3.56 units (2 mg vs. placebo (p < 0.001 for both)	Significant benefits observed on UDPRS motor, ADL, and mental subscales. The symptomatic benefit of rasagiline is comparable with that seen with selegiline and labezamide. No significant differences in adverse events between the placebo and rasagiline groups	Parkinson study group 2002
TEMPO delayed start double-blind, parallel-group, randomized trial of rasagiline as monotherapy in early PD	52 weeks; 371 patients from TEMPO 6-month study. Rasagiline group: 1 or 2 mg for 52 weeks, vs initial placebo group switched to rasagiline after 26 weeks	Doses: 1 mg and 2 mg (early start) or 2 mg (delayed start)	UPDRS improvement: 1.45 units for 2 mg, 1.93 units for 1 mg/day, and 3.75 units for the delayed start group (p = 0.05), rasagiline 1 mg vs 2 mg (p = 0.018)	Patients treated with 1 and 2 mg for 12 months showed less functional decline than those delayed treated for 6 months. The randomized delayed-start design used in this study was intended to separate an immediate symptomatic effect from an effect on desease progression	Parkinson Study Group 2004
LARGO double-blind, parallel-group randomized,placebo controlled study of rasagiline adjunctive to L-dopa therapy.	18 weeks; 687 patients with advanced pD on L-dopa treatment with motor flutuations	Doses: rasagiline 1mg/L-dopa;entacapone 200 mg/L-dopa; placebo/L-dopa	Patients treated with rasagiline or entacapone showed 0.8 h(25%) less “off” time/day (p = 0.0001 for both) compared to placebo; no significant differance between raagiline and entacapone was measured	The “on” time, the CGI and gait freezing were significantly improved. No significant differences in adverse effects between the parallel groups	Rascol et al 2005
PRESTO double-blind, parallel-group, randomized, placebo controlled study of rasagiline adjunctive to L-dopa therapy	26 weeks; 472 patients with advanced PD on L-dopa treatment with motor flutuations	Doses: rasagiline 0.5 mg/L-dopa; rasagiline 1mg/L-dopa; placebo/L-dopa	Rasagiline 0.5 mg had 0.5 h (20%) less “off” time/day (p = 0.02) and 1 mg group had 0.94 h (25%) less “off” time/day (p < 0.001) vs placebo	CGI, UPDRS ADL scores were improved. No differences in adverse effects for rasagiline vs placebo were observed	Parkinson Study Group 2005

Abbreviations: ADL, advanced daily living; CGI, clinical global impression; PD, Parkinson’s disease; UPDRS, Unified Parkinson Disease Rating Scale.

RabeyJMSagiIHubermanMRasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson’s disease: a double-blind study as adjunctive therapy to levodopaClin Neuropharmacol2000233243011575866

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SternMBMarekKLFriedmanJDouble-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson’s disease patientsMov Disord2004199162315300656

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Parkinson study groupA controlled trial of rasagiline in early Parkinson disease: the TEMPO StudyArch Neurol20025919374312470183

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Parkinson study groupA controlled, randomized, delayed-start study of rasagiline in early Parkinson diseaseArch Neurol200461561615096406

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RascolOBrooksDJMelamedERasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomized, double-blind, parallel-group trialLancet20053659475415766996

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Parkinson study groupA randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO studyArch Neurol200562241815710852

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