Monoamine Oxidase Inhibition in Neurological Disorders

Monoamine oxidase inhibition is central to the modulation of monoaminergic neurotransmission and oxidative stress in a spectrum of neurological disorders. Monoamine oxidases are mitochondrial flavoenzymes that catalyse the oxidative deamination of key neurotransmitters—dopamine, serotonin and noradrenaline—yielding aldehydes, hydrogen peroxide and ammonia. Two isoforms, MAO-A and MAO-B, differ in substrate preference and anatomical distribution, underpinning their distinct roles in mood regulation, cognitive function and neurodegeneration. Inhibition of MAOs raises synaptic monoamine levels and mitigates the formation of reactive oxygen species and neurotoxic aldehydes, thereby protecting neuronal integrity and curbing neuroinflammatory cascades. Clinically, irreversible inhibitors such as selegiline and rasagiline have well-established efficacy in Parkinson’s disease, while reversible MAO-A inhibitors like moclobemide are deployed in affective disorders. Recent advances focus on enhancing isoform selectivity to minimise peripheral side effects associated with dietary amines and on the design of multifunctional agents that combine MAO inhibition with anti-inflammatory or neuroprotective actions. Structure–activity relationship analyses and crystallographic insights into active-site topology have guided the rational design of novel scaffolds, including flavonoid derivatives and synthetic analogues. Emerging evidence also links MAO activity to mitochondrial dysfunction and glial activation in Alzheimer’s disease and other neurodegenerative conditions, highlighting the global significance of MAO inhibition beyond classical neurotransmitter regulation.

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Monoamine Oxidase Inhibition in Neurological Disorders publication trend

The graph below shows the total number of articles in monoamine oxidase inhibition in neurological disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Monoamine oxidase (MAO): A mitochondrial flavoenzyme responsible for the oxidative deamination of monoamine neurotransmitters, regulating their synaptic levels and generating reactive by-products.

MAO-A and MAO-B isoforms: Two closely related enzymes that differ in amino acid sequence, substrate preference and tissue distribution, underpinning distinct physiological and pathological roles.

Oxidative deamination: The enzymatic process by which an amine group is removed from a substrate, yielding an aldehyde, hydrogen peroxide and ammonia.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen, such as hydrogen peroxide, that can induce oxidative damage and modulate cell signalling.

Neuroinflammation: The immune-mediated response in the central nervous system characterised by glial activation and release of pro-inflammatory mediators.

References

1. Monoamine oxidases: A missing link between mitochondria and inflammation in chronic diseases ?. Redox Biology (2024).
2. Synthesis and Biological Evaluation of O6-Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases. Antioxidants (2023).
3. Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology. Frontiers in Pharmacology (2016).
4. Sembragiline: A Novel, Selective Monoamine Oxidase Type B Inhibitor for the Treatment of Alzheimer’s Disease. Journal of Pharmacology and Experimental Therapeutics (2017).
5. Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action. Frontiers in Pharmacology (2021).
6. Quercetin and Related Chromenone Derivatives as Monoamine Oxidase Inhibitors: Targeting Neurological and Mental Disorders. Molecules (2019).
7. Analysis of Conserved Active Site Residues in Monoamine Oxidase A and B and Their Three-dimensional Molecular Modeling*. Journal of Biological Chemistry (2002).