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MAO inhibitors were the first line drugs developed for the management of severe depression but most of these were withdrawn from the clinical practice due to their fatal side effects including food-drug interactions.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.
Keywords: Monoamine oxidase, neurological disorders, parkinson's disease, alzheimer’s disease, depression, food drug interactions.
Current Drug Targets
Title:A Perspective on Monoamine Oxidase Enzyme as Drug Target: Challenges and Opportunities
Volume: 18 Issue: 1
Author(s): Bhupinder Kumar, Vivek Prakash Gupta and Vinod Kumar
Affiliation:
Keywords: Monoamine oxidase, neurological disorders, parkinson's disease, alzheimer’s disease, depression, food drug interactions.
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MAO inhibitors were the first line drugs developed for the management of severe depression but most of these were withdrawn from the clinical practice due to their fatal side effects including food-drug interactions.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.
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Cite this article as:
Kumar Bhupinder, Gupta Prakash Vivek and Kumar Vinod, A Perspective on Monoamine Oxidase Enzyme as Drug Target: Challenges and Opportunities, Current Drug Targets 2017; 18 (1) . https://dx.doi.org/10.2174/1389450117666151209123402
DOI https://dx.doi.org/10.2174/1389450117666151209123402 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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