Monoamine Oxidase Inhibitors in Drug Discovery Against Parkinson’s Disease: An Update

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with substantial socioeconomic impact, characterized by the gradual loss of dopaminergic neurons, dopamine deficiency, and pathological processes such as neuroinflammation, oxidative stress, and α-synuclein aggregation. Monoamine oxidases (MAOs) are enzymes responsible for the degradation of neuroactive amines, including dopamine, a neurotransmitter essential for motor, cognitive, and behavioral functions. Among these, MAO-B plays a central role in dopamine metabolism, producing reactive metabolites and oxidative species that contribute to the oxidative stress associated with PD pathophysiology. In this context, MAO-B inhibition has emerged as a promising therapeutic strategy. However, specific limitations, such as motor complications linked to prolonged levodopa use and the adverse effects of currently available MAO inhibitors, remain significant clinical challenges. Methods: A comprehensive literature search was conducted using PubMed and SciFinder databases. Keywords such as “MAO inhibitors”, “Parkinson’s pathology,” and “Parkinson’s disease” were combined with Boolean operators (AND, OR, NOT). The search covered publications from 2010 to 2025. Results: While previous reviews, particularly those by the groups of Guglielmi and Alborghetti, mainly emphasized the clinical use of MAO-B inhibitors and advances in patents, the present review identified approximately 300 compounds synthesized and evaluated as MAO inhibitors, encompassing diverse chemical classes. Among them, selective MAO-B inhibitors exhibited the greatest pharmacological potential, reinforcing the relevance of this isoform as a strategic target in PD therapy. Conclusion: These findings highlight the advances of Medicinal Chemistry in the development of novel MAO-B inhibitors, both as monotherapies for early-stage PD and as adjuvants to levodopa in advanced disease. Collectively, they emphasize the promise of MAO-B inhibitors as candidates for more effective therapeutic interventions in Parkinson’s disease.