MAO-A inhibition

MAO-A inhibition. Blocks monoamine oxidase A, the enzyme that breaks down serotonin, noradrenaline and dietary tyramine. Two separate hazards come off one enzyme: serotonin accumulates (toxicity) and dietary tyramine is no longer destroyed in the gut wall (pressor response).

MAO-B inhibition. Blocks monoamine oxidase B, which preferentially handles dopamine and phenylethylamine. At low, B-selective doses the tyramine hazard is much smaller; selectivity is lost as dose rises.

What acts on it

• Phenelzine — inhibits, strong
  Irreversible; enzyme activity returns only as new enzyme is synthesised, over about two weeks.
• Tranylcypromine — inhibits, strong
  Irreversible and non-selective, and unlike phenelzine it additionally releases noradrenaline in the manner of an amphetamine. That second property is why its pressor reactions can be more abrupt, and why it is the MAOI with the most stimulant-like adverse-effect profile.
• Isocarboxazid — inhibits, strong
  Irreversible and non-selective. The same two-week enzyme-resynthesis rule applies to it as to phenelzine and tranylcypromine, so both the dietary restriction and the washout interval before any serotonergic drug are measured in weeks rather than days.
• Moclobemide — inhibits, moderate
  Reversible and competitive — tyramine displaces it. The tyramine pressor dose is raised only about 2–4 fold, versus roughly 10–50 fold for irreversible MAOIs, and the classic diet is not generally required at standard doses.
• Selegiline (oral) — inhibits, strong
• Selegiline transdermal system — inhibits, moderate
  Central MAO-A inhibited; INTESTINAL MAO-A largely spared, which is the mechanistic reason the diet is not required at 6 mg/24 h.
• Rasagiline — inhibits, strong
• Linezolid — inhibits, moderate
  Reversible. Serotonin toxicity has been reported repeatedly when it is started in someone already on a serotonergic antidepressant.
• Methylene blue (methylthioninium chloride) — inhibits, strong
  Given intravenously in theatre for vasoplegia and parathyroid localisation, and for methaemoglobinaemia — settings where nobody is reviewing the patient's antidepressant. Serotonin toxicity following intraoperative methylene blue in a patient on an SSRI is a recognised event, and the exposure is a single dose nobody wrote on a medication list.
• Harmala alkaloids (harmine, harmaline, tetrahydroharmine) — inhibits, strong
  Harmine and harmaline are potent competitive MAO-A inhibitors in human tissue; tetrahydroharmine additionally inhibits serotonin reuptake.
• Ayahuasca (hoasca, daime) — inhibits, strong
  The brew delivers MAO-A inhibition and a direct 5-HT agonist in the same cup, by design — that is what makes it orally active. It therefore carries the serotonergic hazard from both directions at once, which is the specific reason the ayahuasca harm-reduction literature is emphatic about SSRI washout before a session.
• Nutmeg (myristicin, elemicin) — inhibits, weak
  Truitt et al. (1963) demonstrated MAO inhibition by myristicin and nutmeg. The evidence is old and largely non-human; treat it as a documented signal of uncertain human magnitude, not as an equivalent of a prescribed MAOI. Marked here deliberately as WEAK rather than dropped, because a weak documented signal in a kitchen spice is worth a reader knowing about.

What is affected by it

• Nothing in this dataset.

Recognising serotonin toxicity

Last reviewed 2026-09-09. All interaction pages.