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The Role of Monoamine Oxidase B Inhibitors in the Treatment of Parkinson's Disease-An Update

Journal

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
Volume 22, Issue 3, Pages 329-352

Publisher

BENTHAM SCIENCE PUBL
DOI: 10.2174/1871527321666211231100255

Keywords

Parkinson's disease; monoamine oxidase B inhibitor; selegiline; rasagiline; safinamide; neuroprotective

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Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by reduced dopamine levels. Inhibitors of monoamine oxidase B (MAO-B) are used to alleviate symptoms by preserving functional levels of dopamine. The first MAO-B inhibitor used therapeutically was selegiline, followed by rasagiline, which has superior efficacy. Safinamide, a reversible MAO-B inhibitor, was recently approved as an add-on therapy for mid- or late-stage PD. MAO-B inhibitors may have potential neuroprotective and disease modifying effects, but further investigation is needed.
Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by reduced dopamine levels in the substantial nigra. This may lead to typical motor features such as bradykinesia, resting tremors and rigid muscles, as well as non-motor symptoms such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, and sensory disturbances. Inhibitors of monoamine oxidase B (MAO-B) are used to alleviate symptoms by reducing monoamine oxidase-catalysed degradation of dopamine; hence, preserving functional levels of dopamine. The very first MAO-B inhibitor used therapeutically was selegiline, followed by rasagiline, its indane derivative which has superior efficacy and selectivity. Both inhibitors can be used as monotherapy or in combination with other anti- Parkinson drugs. Safinamide, a reversible MAO-B inhibitor that utilises both dopaminergic and non-dopaminergic mechanisms, was recently approved by the European Medicines Agency (EMA) (2015) and U.S. FDA (2017) as an add-on therapy for patients with mid- or late-stage Parkinson's disease. Furthermore, MAO-B inhibitors were found to be associated with potential neuroprotective and disease modifying effects. However, evidence of their efficacy and role in PD models is scarce and warrants further investigation.

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