Duarte Pablo, Cuadrado Antonio, León Rafael
Instituto Teófilo Hernando y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain.
Handb Exp Pharmacol. 2021;264:229-259. doi: 10.1007/164_2020_384.
Monoamine oxidases (MAOs) are involved in the oxidative deamination of different amines and neurotransmitters. This pointed them as potential targets for several disorders and along the last 70 years a wide variety of MAO inhibitors have been developed as successful drugs for the treatment of complex diseases, being the first drugs approved for depression in the late 1950s. The discovery of two MAO isozymes (MAO-A and B) with different substrate selectivity and tissue expression patterns led to novel therapeutic approaches and to the development of new classes of inhibitors, such as selective irreversible and reversible MAO-B inhibitors and reversible MAO-A inhibitors. Significantly, MAO-B inhibitors constitute a widely studied group of compounds, some of them approved for the treatment of Parkinson's disease. Further applications are under development for the treatment of Alzheimer's disease, amyotrophic lateral sclerosis, and cardiovascular diseases, among others. This review summarizes the most important aspects regarding the development and clinical use of MAO inhibitors, going through mechanistic and structural details, new indications, and future perspectives. Monoamine oxidases (MAOs) catalyze the oxidative deamination of different amines and neurotransmitters. The two different isozymes, MAO-A and MAO-B, are located at the outer mitochondrial membrane in different tissues. The enzymatic reaction involves formation of the corresponding aldehyde and releasing hydrogen peroxide (HO) and ammonia or a substituted amine depending on the substrate. MAO's role in neurotransmitter metabolism made them targets for major depression and Parkinson's disease, among other neurodegenerative diseases. Currently, these compounds are being studied for other diseases such as cardiovascular ones.
单胺氧化酶（MAOs）参与不同胺类和神经递质的氧化脱氨作用。这使其成为多种疾病的潜在靶点，在过去70年里，已开发出各种各样的MAO抑制剂作为治疗复杂疾病的成功药物，是20世纪50年代末首批获批用于治疗抑郁症的药物。两种具有不同底物选择性和组织表达模式的MAO同工酶（MAO-A和MAO-B）的发现，带来了新的治疗方法以及新型抑制剂的开发，如选择性不可逆和可逆的MAO-B抑制剂以及可逆的MAO-A抑制剂。值得注意的是，MAO-B抑制剂是一类经过广泛研究的化合物，其中一些已获批用于治疗帕金森病。它们在治疗阿尔茨海默病、肌萎缩侧索硬化症和心血管疾病等方面的进一步应用正在研发中。本综述总结了MAO抑制剂开发和临床应用的最重要方面，涵盖作用机制和结构细节、新适应症以及未来展望。单胺氧化酶（MAOs）催化不同胺类和神经递质的氧化脱氨作用。两种不同的同工酶MAO-A和MAO-B位于不同组织的线粒体外膜。酶促反应涉及相应醛的形成，并根据底物释放过氧化氢（HO）和氨或取代胺。MAO在神经递质代谢中的作用使其成为重度抑郁症和帕金森病等其他神经退行性疾病的靶点。目前，这些化合物正在针对心血管疾病等其他疾病进行研究。
