A Perspective on Monoamine Oxidase Enzyme as Drug Target: Challenges and Opportunities

Abstract

The monoamine oxidase (MAO) enzyme is responsible for the deamination of monoamine neurotransmitters and regulates their concentration in the central and peripheral nervous systems. Imbalance in the concentration of neurotransmitters in the brain and central nervous system is linked with the biochemical pathology of various neurogenic disorders. Irreversible MAO inhibitors were the first line drugs developed for the management of severe depression but most of these were withdrawn from the clinical practice due to their fatal side effects including food-drug interactions. New generations of MAO inhibitors were developed which were reversible and selective for one of the enzyme isoform and showed improved pharmacological profile. The discovery of crystal structure of MAO-A & MAO-B isoforms helped in understanding the drug-receptor interactions at the molecular level and designing of ligands with selectivity for either of the isoforms. The current article provides an overview on the MAO enzyme as potential drug target for different disease states. The article describes catalytic mechanism of MAO enzyme, crystal structures of the two MAO isoforms, traditional MAO inhibitors and various problems associated with their use, new developments in the MAO inhibitors and their potential as therapeutic agents especially in neurological disorders.