Monoamine Oxidase Inhibitors: From Classic to New Clinical Approaches
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
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Contents 1 Overview 2 Structure and Binding Site of MAO 2.1 Mechanisms of MAO Catalysis and Inhibition 3 Therapeutic Value of MAO Inhibitors 3.1 Affective Diseases 3.2 Parkinson’s Disease 3.3 Other Neurodegenerative Disorders 3.4 Cardiac Diseases 4 Summary and Future Prospects References
P. Duarte 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 A. Cuadrado 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 R. León (*) 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 Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), Madrid, Spain e-mail: [email protected] # Springer Nature Switzerland AG 2020 Handbook of Experimental Pharmacology, https://doi.org/10.1007/164_2020_384
P. Duarte et al.
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
Serotonin (5-HT) rMAOAi
Adrenaline, Dopamine, Noradrenaline, Tryptamine, Tyramine
Benzylamine, Phenylethylamine rMAOBi
rMAOi MAOA
Depression
iMAOi Aldehyde NH3 or substituted amine H2O2
MAOB
iMAOBi Parkinson Depression
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 diff
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