Multi-target monoamine oxidase-B (MAO-B) inhibitors in the treatment of Parkinson’s disease

Parkinson’s disease (PD) is a fast-advancing disorder of the nervous system, ranking only behind Alzheimer’s disease as the most prevalent neurodegenerative condition associated with aging. Its incidence increases with age – being relatively rare in people in their fifties and sixties but much more frequent in individuals older than eighty-five. Although extensive research over the past two centuries has been carried out to uncover the causes and mechanisms behind PD, its exact origins and underlying biology remain unclear. In the management of PD, monoamine oxidase-B (MAO-B) inhibitors are among the most frequently used drugs. In recent years, the multitarget-directed ligand (MTDL) approach has gained attention in neuropharmacology. This strategy involves designing compounds capable of acting on multiple biological pathways implicated in neurodegeneration at once, rather than targeting a single mechanism. This review summarizes recent progress in the development of such multi-target drugs for Parkinson’s disease. It begins with an overview of PD, then discusses the primary mechanisms involved in its pathogenesis, current treatment options, and the emergence of multi-target therapies – with a particular focus on MAO-B inhibitors. For each group of compounds discussed, the relationship between their chemical structure and biological activity is examined and analyzed.