History and Therapeutic Use of MAO-A Inhibitors: A Historical Perspective of MAO-A Inhibitors As Antidepressant Drug

Abstract

Since the first generation of MAO inhibitors was developed, more than fifty years ago, this family of drugs has been ups and downs over the last decades. Actually, interest in MAO inhibitors is reviving and the emergence of new advances in the rational design of molecules and new techniques to predict the in vivo behavior has encouraged the research for new drugs with therapeutic potential in this area. The classic MAOIs have been widely used as antidepressants during the two decades after its introduction in clinic. Based on observations made on MAO inhibition by these drugs, it has been postulated hypothesis that have contributed to a better understanding of the mechanism and management of depressive disorders. However, exaggerated concerns about food and drug interactions relegated these drugs from the pharmaceutical landscape. The correct interpretation and the contextualization of side effects and the recent research findings, in which MAO selective inhibitors appear as promising agents in the treatment of emerging and high prevalence diseases, are placing these drugs again into the scientific and pharmacological focus.

Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the Development of Monoamine Oxidase Inhibitors

“…Monoamine oxidase inhibitors (MAOIs) are best known for their antidepressant effects, but their recently elucidated role in influencing oxidative stress and apoptosis ( Ou et al, 2006a ; Fitzgerald et al, 2007 ; Johnson et al, 2011 ) has led to investigations of MAOIs for the treatment of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Disease ( Maruyama et al, 2003 ; Youdim et al, 2006 ). This resurgence in MAOI development has led to compounds with improved tolerability profiles compared to the initial irreversible MAOIs, particularly in regard to tyramine-induced hypertension and dietary restrictions ( Yanez et al, 2012 ). This improved tolerability is being achieved through several strategies, which include greater selectivity for either monoamine oxidase-A (MAO-A) or monoamine oxidase-B (MAO-B), reversible binding to MAO, and/or use of a pro-drug design in which the initial drug is metabolized to the active drug in the brain, resulting in an increased ratio of brain-to-gut concentration of the active drug ( Maruyama et al, 2003 ; Gal et al, 2005 ; Avramovich-Tirosh et al, 2007 ).…”

Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines

“…Unfortunately, MAO-inhibitors cannot discriminate among the different MAOs, and their overall effect results in high concentrations of tyramine that can cause hypertensive crises, brain hemorrhage and sometimes death ( Pessione et al, 2009 ). Since tyramine is the biogenic amine most frequently found in cheese (due to the referred high tyrosine content of dairy products) this syndrome is also called “cheese reaction.” For the reasons explained above, MAOI development has led to compounds with improved tolerability profiles compared to the initial irreversible MAOIs, particularly in regard to tyramine-induced hypertension and dietary restrictions ( Yanez et al, 2012 ). The huge number of non-controlled autochthonous bacteria involved in cheese manufacturing and the accidental contamination by unwanted strains during storage render cheese a risky food for tyramine ingestion, although starters are accurately typed.…”

A Proteotranscriptomic-Based Computational Drug-Repositioning Method for Alzheimer’s Disease

“…It is a selective irreversible MAO-B inhibitor in clinical doses, whereas it also inhibits MAO-A in larger doses (Fowler et al, 2015). Iproniazid, another MAO inhibitor, is used as an antidepressant drug (Yáñez et al, 2012). Several mechanisms have been proposed to account for involvement of MAO in AD pathology such as cognitive dysfunction via destroying cholinergic neurons and the formation of Aß aggregation or NFTs (Thomas, 2000;Huang et al, 2012;Mousseau and Baker, 2012;Cai, 2014;Quartey et al, 2018).…”