monoamine oxidase

MAO is located on the outer mitochondrial membrane in neurons, liver, and gut, and breaks down monoamines into their corresponding aldehydes, which are then further metabolized (often by aldehyde dehydrogenase) to inactive acids or alcohols. MAO-A preferentially metabolizes serotonin, norepinephrine, and dopamine, while MAO-B preferentially metabolizes dopamine and phenylethylamine. MAO-A inhibitors (e.g., older nonselective MAOIs like phenelzine, tranylcypromine, isocarboxazid) increase synaptic monoamines and are used for atypical depression and anxiety disorders refractory to other treatments; selegiline is a selective MAO-B inhibitor used adjunctively in Parkinson's disease to reduce dopamine breakdown. A critical clinical concern with nonselective MAOIs is dietary tyramine interaction: tyramine is normally metabolized by gut/liver MAO, and when this is inhibited, ingestion of tyramine-rich foods (aged cheese, cured meats, red wine, fermented foods) can precipitate a hypertensive crisis due to massive release of stored norepinephrine from sympathetic terminals. Additionally, combining MAOIs with serotonergic drugs (SSRIs, SNRIs, meperidine, dextromethorphan, triptans) risks serotonin syndrome due to excessive serotonergic activity—characterized by hyperthermia, autonomic instability, clonus, and altered mental status; a washout period of at least 2 weeks (5 weeks for fluoxetine due to its long half-life) is required when switching between these drug classes. MAO activity is also relevant in genetic studies: mutations in MAOA have been linked (controversially) to aggressive behavior phenotypes (e.g., Brunner syndrome). Understanding MAO is essential for boards given its central role in both psychiatric pharmacology and movement disorder treatment.