monoamine oxidase inhibitor
A monoamine oxidase inhibitor (MAOI) raises neurotransmitter levels not by blocking a pump but by disabling the enzyme that destroys them. Picture monoamine neurotransmitters being constantly nibbled away by a clean-up enzyme; an MAOI ties that enzyme's hands, so more of the messengers survive and accumulate.
Monoamine oxidase is the enzyme that breaks down monoamine neurotransmitters — serotonin, norepinephrine, and dopamine — both inside neurons and in tissues like the gut. By inhibiting it, an MAOI lets these neurotransmitters build up, which is the basis for its antidepressant effect. There are two isoforms: MAO-A (more involved in serotonin and norepinephrine) and MAO-B (targeted by selegiline in Parkinson's disease).
MAOIs such as phenelzine and tranylcypromine were among the first antidepressants. They are highly effective but now used mainly for depression that has not responded to other drugs, because of their interaction risks.
Two dangers stand out. Because MAO in the gut normally destroys dietary tyramine, an MAOI lets tyramine flood the circulation and trigger a hypertensive crisis after foods like aged cheese — the famous 'cheese reaction.' And combining an MAOI with other serotonin-raising drugs can cause life-threatening serotonin syndrome, so washout periods between such drugs are mandatory.
A patient on an MAOI is warned to avoid aged cheese, cured meats, and certain fermented foods, because the tyramine they contain can no longer be broken down and may spike blood pressure dangerously.
The dietary tyramine restriction is the hallmark caution of MAOI therapy.
MAOIs and reuptake inhibitors both increase neurotransmitter levels but at different steps — breakdown versus reuptake — and because both push in the same direction, stacking them can cause dangerous serotonin syndrome.