OBJECTIVE: RESULTS: Data from 63 clinical and laboratory studies were analyzed. Based on the results from those studies, we concluded that
rasagiline PO QD, at the therapeutic dosage range of 0.5 to 1 rag/d, is effective and well tolerated and completely, selectively, and specifically inhibited
MAO-B. Pharmacologically,
rasagiline was found to be < or =10-fold more potent than
selegiline and was not metabolized to
amphetamine derivatives.
Rasagiline was effective both as monotherapy in early PD and as adjunctive treatment in patients with advancing PD and motor fluctuations. As monotherapy,
rasagiline provided modest yet clinically meaningful benefit. A randomized, double-blind, placebo-controlled study found that, after 26 weeks of treatment, the adjusted effect size for total Unified Parkinson's Disease Rating Scale score was -4.20 (95% CI, -5.66 to -2.73) for
rasagiline 1 mg/d versus placebo (P < 0.001). Preliminary long-term data from an open-label study suggest a sustained therapeutic advantage when
rasagiline is initiated early (before the need for
dopaminergic agents) rather than later. In patients with more advanced disease who received treatment with
dopaminergic agents,
rasagiline and
entacapone were associated with reductions of "off" time significantly greater than placebo (-1.18 and -1.2 vs 0.4 hour; both, P < or = 0.001).
Rasagiline was well tolerated in younger (aged <;70 years) and older (aged > or =70 years) patients with early or advanced PD. Pharmacologically,
rasagiline has the potential to augment the vasopressor effects of diet-derived
tyramine (ie, the "cheese reaction"). However, clinical challenge studies of
tyramine have found this unlikely to occur even with ingestion of supraphysiologic amounts of
tyramine. In experimental models,
rasagiline has been found to have neuroprotective properties that may be independent of
MAO-B inhibition.
CONCLUSIONS: