Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action

Article from 30 April 2021

frontiersin.org/articles/10...

Concluding Remarks and Future Perspectives

MAO inhibitors have a long history of successful clinical use to manage CNS diseases such as depression, Parkinson’s, and Alzheimer’s. There is also an abundance of literature showing that MAO-A, MAO-B, and MAO-A/B inhibitors have CNS and non-CNS-associated anti-inflammatory effects in diseases of epithelial and soft and hard connective tissues. These data support their anti-inflammatory effects, but a concerted effort is needed to help focus which chronic inflammatory diseases are the best targets to select for expanded clinical testing. In conjunction, examining MAO-A and MAO-B expression in healthy and affected tissues and in recruited immune cells is needed to better understand the role(s) of MAOs in disease pathogenesis and will help to direct the selection of the most appropriate MAO inhibitors to test. Associated with these studies is a need to expand mechanistic studies as well. MAO inhibitors have broad-reaching cellular effects. They reduce metabolic end products such as hydrogen peroxide and aldehyde, and this reduction clearly has anti-inflammatory effects. Notwithstanding, MAO inhibitors also increase cellular and pericellular catecholamine levels. Catecholamines such as dopamine, norepinephrine, and epinephrine can be synthesized, stored, and released by immune and non-immune cells, and catecholamine signaling is associated with a reduction of inflammation. MAO inhibitors can increase both intracellular and extracellular catecholamines, and both can impact signaling. An increase in intracellular catecholamines may drive receptor-independent signaling. Alternatively, an increase in pericellular catecholamines may signal in a receptor-dependent manner. The diverse adrenergic and dopaminergic receptor families have different and divergent effects on inflammation and selective stimulation through their respective subtypes, and can dramatically alter the inflammatory response. When MAO inhibitors are being tested for therapeutic efficacy in inflammatory disease models, it is critical to expand mechanistic studies to examine these divergent signaling mechanisms. The prospect of either repurposing existing or developing novel MAO inhibitors for the management of chronic inflammatory diseases is a promising and exciting area of investigation.

[Boscoejean]

"The most significant risk associated with the use of MAOIs is the potential for drug interactions with over-the-counter, prescription, or illegally obtained medications, and some dietary supplements (e.g., St. John's wort, tryptophan). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid (e.g. adrenaline (epinephrine) dosage should be reduced by 75%, and duration is extended.)[23]"en.wikipedia.org/wiki/Monoa...