Rasagiline

Rasagiline is a second-generation potent, irreversible and selective inhibitor of monoamine.-oxidase type B (MAO-B), which has been evaluated for the treatment of Parkinson's disease. Rasagiline also possesses neuroprotective properties that are independent of its MAO inhibitory activity. Unlike selegiline, rasagiline has no amphetamine-like metabolites and its major metabolite, 1-(R)-aminoindan, has demonstrated favourable pharmacological activity in experimental studies. Rasagiline has shown significant beneficial effects as monotherapy in the treatment of early Parkinson's disease. Monotherapy with rasagiline 1 or 2mg once daily significantly attenuated the worsening of symptoms, compared with placebo, in patients with early Parkinson's disease in a randomised, double-blind trial (n = 404). Furthermore, patients treated with rasagiline for 12 months had less functional decline than patients whose treatment was delayed for 6 months (n = 371). In patients with moderate-to-advanced disease receiving background therapy with levodopa and additional anti-parkinsonian medications (n = 1159), rasagiline 0.5 or 1mg once daily reduced the daily 'off' time by 0.49-0.94 hours relative to that in placebo recipients in two randomised, double-blind trials. The efficacy of rasagiline 1mg once daily was similar to entacapone 200mg administered with each levodopa dose. Rasagiline was generally well tolerated in clinical trials as both monotherapy and when administered with other antiparkinsonian drugs. Adverse events with rasagiline were generally similar in frequency to those seen in placebo or entacapone recipients. Parkinson's disease is a progressive neurodegenerative disorder primarily affecting the elderly population,([1,2]) although young-onset disease may occur in individuals aged <40 years.([1,3]) The prevalence of the disease increases with age and is generally similar in males and females.([4-7]) Consolidated data from epidemiological studies published during the 1990s have shown an overall prevalence rate in six European countries of 1.8% for population aged >65 years; the prevalence increased from 0.6% in those aged 65-69 years to 2.6% in those greater than or equal to80 years of age.([7]) None of the current treatments is proven to arrest or even delay the neuronal loss in Parkinson's disease, although several classes of drugs have shown neuroprotective/neurorescue activities in experimental studies.([1,8,9]) Consequently, pharmacotherapy of the disease has been essentially symptomatic in nature, with levodopa being the mainstay for more than 3 decades.([1,2]) However, several problems have been recognised with long-term levodopa treatment, including motor fluctuations, dyskinesia and, possibly, neurotoxicity.([2]) Along with the development of new strategies to improve levodopa therapy (such as catechol-O-methyl transferase inhibitors, e.g. entacapone), alternative treatment options have become available for Parkinson's disease, including dopamine agonists (e.g. ropinirole) and monoamine-oxidase (MAO) type B inhibitors (e.g. selegiline), that can be used alone or in conjunction with levodopa therapy.([2]) The focus of this review is a second-generation MAO-B inhibitor, rasagiline (TVP-1012) [Agilect((R)) Azilect((R))](1), a propargylamine derivative that has shown efficacy in the treatment of all stages of Parkinson's disease.