摘要
单胺氧化酶(MAO)负责单胺类神经递质的去氨基化,并调整它们在中枢和外周神经系统的浓度。大脑和中枢神经系统中神经递质浓度的不平衡与许多神经性生物化学途径失调有关。不可逆的MAO抑制剂是为急剧下调(MAO)所研发的第一批药物,但因大部分(抑制剂)都有致命的副作用,包括食物-药物相互反应而在临床实验被中止。新一代MAO抑制剂被研发出来了,它们对某一酶亚型具有选择性并且可逆,表现出改进的药理作用。MAO-A和MAO-B亚型晶体结构的发现帮助(人们)在分子层面上理解了药物-受体相互作用,人民以此为每一个亚型设计了选择性配体。这篇综述概述了MAO酶作为不同疾病情形的药物靶点的可能性。这篇文章描述了MAO酶的催化机理,两种MAO亚型的晶体结构,传统的MAO抑制剂和它们使用所导致的问题,MAO抑制剂的新进展和它们作为神经性失调治疗药物的可能性。
关键词: 单胺氧化,神经性失调,帕金森病,阿尔茨海默症,下调,食物药物相互作用
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, Vinod Kumar
Affiliation:
关键词: 单胺氧化,神经性失调,帕金森病,阿尔茨海默症,下调,食物药物相互作用
摘要: 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MAO inhibitors were the first line drugs developed for the management of severe depression but most of these were withdrawn from the clinical practice due to their fatal side effects including food-drug interactions.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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Bhupinder Kumar, Vivek Prakash Gupta, Vinod Kumar , 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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