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Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches

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Reactive Oxygen Species

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 264))

Abstract

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.

Graphical Abstract

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 (H2O2) 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.

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Authors and Affiliations

  1. Instituto Teófilo Hernando y Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

    Pablo Duarte & Rafael León

  2. Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain

    Pablo Duarte & Rafael León

  3. Departmento de Bioquímica, Facultad de Medicina, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ UAM-CSIC, Universidad Autónoma de Madrid, Madrid, Spain

    Antonio Cuadrado

  4. Instituto de Química Médica, Consejo Superior de Investigaciones CientÚficas (IQM-CSIC), Madrid, Spain

    Rafael León

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  1. Pablo Duarte
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  2. Antonio Cuadrado
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  3. Rafael León
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Correspondence to Rafael León .

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Editors and Affiliations

  1. Department of Pharmacology and Personalised Medicine, Maastricht University, Maastricht, The Netherlands

    Harald H. H. W. Schmidt

  2. Brighton and Sussex Medical School, Brighton, UK

    Pietro Ghezzi

  3. Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain

    Antonio Cuadrado

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Duarte, P., Cuadrado, A., León, R. (2020). Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches. In: Schmidt, H.H.H.W., Ghezzi, P., Cuadrado, A. (eds) Reactive Oxygen Species . Handbook of Experimental Pharmacology, vol 264. Springer, Cham. https://doi.org/10.1007/164_2020_384

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