MAOinhibiting

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that block the activity of the enzymes monoamine oxidase A and monoamine oxidase B, which normally degrade neurotransmitters such as serotonin, norepinephrine, and dopamine. By preventing the breakdown of these biogenic amines, MAOIs increase their availability in the brain and peripheral tissues, thereby exerting therapeutic effects.

The first MAOIs were introduced in the 1950s for the treatment of depression. Early compounds such as phenelzine and tranylcypromine were irreversible inhibitors, forming covalent bonds with the enzyme active sites. Subsequent development yielded reversible inhibitors that bind transiently, offering a safer side‑effect profile. Additionally, selective MAO‑B inhibitors such as selegiline and rasagiline selectively inhibit MAO‑B at therapeutic doses, and are primarily used in Parkinson’s disease and, in some jurisdictions, as adjunct antidepressants.

MAOIs remain an important option for treatment‑resistant major depressive disorder, atypical depression, and certain anxiety disorders. In Parkinson’s disease, selective MAO‑B inhibition slows the breakdown of dopamine and reduces the formation of toxic metabolites. In psychiatry, phenelzine and tranylcypromine are sometimes used when selective serotonin reuptake inhibitors (SSRIs) are ineffective.

The primary limitation to widespread use of irreversible MAOIs is the risk of hypertensive crisis. This occurs when phenethylamine‑containing foods (such as aged cheese, cured meats, and fermented beverages) or sympathomimetic drugs are taken concurrently. Reversible MAO‑A inhibitors, such as moclobemide, have a lower risk of dietary interaction. Other adverse effects include orthostatic hypotension, insomnia, and mild neurotoxicity at high doses.

Because of drug–drug and food interactions, MAOIs require careful patient education and monitoring. Nonetheless, their unique mechanism of action provides therapeutic benefits in conditions that are refractory to other pharmacologic classes.