MAOI

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant and antiparkinsonian medications that inhibit the enzyme monoamine oxidase, which normally breaks down monoamines such as serotonin, norepinephrine, and dopamine. In humans, the enzyme exists as two isoforms, MAO-A and MAO-B, distributed in brain and peripheral tissues. By inhibiting these enzymes, MAOIs increase synaptic levels of monoamines, potentially improving mood and motor function. Irreversible MAOIs covalently bind to the enzyme and require new enzyme synthesis to restore activity, while reversible inhibitors allow normal function to resume after clearance.

Classic MAOIs include irreversible, nonselective agents such as phenelzine, isocarboxazid, and tranylcypromine. Reversible inhibitors of MAO-A (RIMA) include moclobemide, which are generally associated with fewer dietary restrictions. MAO-B inhibitors such as selegiline and rasagiline are used primarily in Parkinson’s disease; at different doses, these can vary in selectivity for MAO-B versus MAO-A.

Clinical use and considerations: MAOIs are now less commonly used for major depressive disorder due to dietary and drug interactions, but may be prescribed for treatment-resistant depression or certain atypical presentations. They can also be used in Parkinson’s disease as monotherapy or with levodopa. Dietary and drug interactions are a major consideration; foods rich in tyramine (such as aged cheeses and cured meats) can trigger hypertensive crises with nonselective or irreversible MAOIs. Interactions with sympathomimetic drugs, serotonergic medications, and some anesthetics increase risks of hypertensive episodes or serotonin syndrome.

Adverse effects commonly include orthostatic hypotension, weight gain, sleep disturbances, and sexual dysfunction. Careful monitoring and appropriate washout periods are essential when switching therapies.