An updated patent review on monoamine oxidase (MAO) inhibitors

ABSTRACT

Introduction

Monoamine oxidase (MAO) inhibitors are currently used as antidepressants (selective MAO-A inhibitors) or as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). The research within this field is attracting attention due to their crucial role in the modulation of brain functions, mood, and cognitive activity, and monoamine catabolism.

Areas covered

MAO inhibitors (2018–2021) are discussed according to their chemotypes. Structure–activity relationships are derived for each chemical scaffold (propargylamines, chalcones, indoles, benzimidazoles, (iso)coumarins, (iso)benzofurans, xanthones, and tetralones), while the chemical entities were divided into newly synthesized molecules and natural metabolites. The mechanism of action and type of inhibition are also considered. Lastly, new therapeutic applications are reported, which demonstrates the clinical potential of these inhibitors as well as the possibility of repurposing existing drugs for a variety of diseases.

Expert opinion

MAO inhibitors here reported exhibit different potencies and isoform selectivity. These compounds are clinically licensed for multi-faceted neurodegenerative pathologies due to their ability to also act against other relevant targets (cholinesterases, inflammation, and oxidative stress). Moreover, the drug repurposing approach is an attractive strategy by which MAO inhibitors may be applied for the treatment of prostate cancer, inflammation, vertigo, and type 1 diabetes.

KEYWORDS:

• Alzheimer’s disease
• depression
• multi-target inhibitors
• monoamine oxidase
• natural products
• parkinson’s disease

Article highlights

• Newly synthesized molecules and naturally-occurring plant metabolites were licensed as MAO inhibitors

• Chromone derivatives were the most investigated compounds to obtain selective and potent MAO-B inhibitors

• Most of the tested natural compounds were endowed with promising dual MAO/ChE inhibition for multi-functional diseases

• Drug repositioning of MAO inhibitors was studied for innovative therapeutic options

• The in-depth knowledge of natural MAO-A inhibitors could prevent/limit the risk of drug–food interactions

Funding

This paper was not funded.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.