Monoamine Oxidase Inhibition for the Treatment of Neurodegenerative Diseases: Rationale, Assay Methodologies, and Reference Compounds

Monoamine oxidases (MAOs) A and B are key enzymes involved in the metabolism of amine neurotransmitters as well as exogenous amine-containing substances. Since their characterization in the 1960s, they represent a pharmacological target for the discovery of small molecular inhibitors, especially as antidepressants and antiparkinsonian drugs. The development of in vitro/in vivo assays has paralleled such interest allowing the setup of fast and reliable screening methods herein described. Hence, a huge number of potent and selective inhibitors have been discovered, although only in some cases reaching the pharmaceutical market. A renewed interest has emerged with the so-called multitarget approach, combining multiple biological activities in a single molecular entity, speeding up the screening of MAO inhibitors endowed with additional activities for the treatment of neurodegenerative diseases.