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Published online: 17 October 2014
© Springer International Publishing Switzerland 2014
Abstract Rasagiline (Azilect®) is an oral, second-generation, selective, irreversible monoamine oxidase-B (MAO-B) inhibitor approved in the US for the treatment of Parkinson's disease. In randomized, controlled trials, oral rasagiline 1 mg once daily was superior to placebo in the symptomatic treatment of early Parkinson's disease, both as monotherapy or as an adjunct to dopamine agonists. Comparisons of early-start and delayed-start treatment suggested a disease-modifying effect for rasagiline, but the results were equivocal. Rasagiline 0.5 or 1 mg/day was also superior to placebo as adjunctive therapy to levodopa in Parkinson's disease patients with motor fluctuations. Rasagiline was generally well tolerated in clinical trials, displaying a placebo-like tolerability profile in several studies. Cost-utility studies predicted that rasagiline, either as monotherapy or adjunctive therapy, would be a cost-effective treatment option. Therefore, oral rasagiline is a valuable therapeutic option for use in all stages of Parkinson's disease.
1 Introduction
Parkinson's disease is a progressive, degenerative neuro- logical disorder characterized pathologically by the selec- tive loss of dopaminergic neurons in the substantia nigra pars compacta and the intracellular accumulation of Lewy bodies [1-3]. The loss of dopamine-producing neurons leads to the characteristic motor symptoms (e.g. bradyki- nesia, hypokinesia, muscle rigidity, resting tremor and postural instability) of Parkinson's disease [1-3]. Patients also experience non-motor symptoms (e.g. autonomic dysfunction, orthostatic hypotension, dementia, depression, anxiety and sleep disturbances) [1-3]. While dopaminergic regions of the brain are the focus early in the disease process, non-dopaminergic regions of the brain are involved later in the disease course [2]. The prevalence of Parkinson's disease increases with age; the disease affects xl % of the population aged >60 years. While some Parkinson's disease cases are known to have an hereditary origin, most (90 %) are idiopathic [2].
There are no definitive disease-modifying or neuropro- tective therapies available for Parkinson's disease [1, 2]. Initial therapy generally focuses on restoring striatal dopamine to control motor symptoms and the approved drug classes most commonly used for this purpose, in order of potency, are levodopa, dopamine agonists (e.g. pram- ipexole and ropinirole) and monoamine oxidase (MAO)-B inhibitors (e.g. selegiline and rasagiline) [1, 2].
MAO, which is classified as type A or B, breaks down biogenic amines, including neurotransmitters [4,...