Pharmacology · Monoamine oxidase inhibitors (MAOIs)
Phenelzine !
An MAO inhibitor antidepressant for depression that has not responded to other drugs. Foods rich in tyramine and many medicines can cause dangerous reactions.
Updated 2026-11-01
The figure shows clorgyline, an irreversible MAO-A inhibitor, bound next to the FAD cofactor in the active site of human MAO-A; no structure with phenelzine is available.
Mechanism of action
Phenelzine, a hydrazine, is a potent inhibitor of monoamine oxidase, the mitochondrial enzyme that breaks down serotonin, norepinephrine and dopamine. Neurons then store and release more monoamine. MAO in the gut wall and liver also stops destroying tyramine from food, which is the basis of the dangerous dietary interaction.
- Phenelzine inhibits MAO-A and MAO-B
- Serotonin, norepinephrine and dopamine are broken down less
- Neurons store and release more monoamine
- In the gut and liver, dietary tyramine is no longer destroyed
Pharmacokinetics
- Absorption
- By mouth; peak levels within about an hour
- Metabolism
- Mainly oxidised by MAO itself; acetylation is a minor pathway
- Elimination
- As phenylacetic acid metabolites in the urine
- Half-life
- About 11.6 hours after a single dose, but the enzyme stays inhibited much longer; food and drug restrictions continue for two weeks after stopping
Indications
- Depression with «atypical» features (mixed anxiety, phobias, hypochondriacal symptoms) that has not responded to more commonly used antidepressants
Adverse effects
Common
- Orthostatic hypotension and dizziness
- Weight gain and oedema
- Sexual dysfunction (anorgasmia, ejaculatory problems)
- Insomnia or drowsiness, tremor, muscle twitching
- Dry mouth, constipation, raised transaminases
Contraindications
- Pheochromocytoma, congestive heart failure, liver disease or abnormal liver tests, severe kidney disease
- Sympathomimetics (amphetamines, cocaine, methylphenidate, decongestants, epinephrine) and levodopa
- Meperidine, dextromethorphan, other MAOIs, bupropion, buspirone and serotonergic antidepressants; 14 days between stopping phenelzine and starting these
- Foods and drinks rich in tyramine
- Elective surgery under general anaesthesia (label: phenelzine stopped at least 10 days before)
Key interactions
- Aged cheese, cured or fermented meats and fish, sauerkraut, broad bean pods, yeast or meat extracts, beer and wine
- Hypertensive crisis from tyramine
- SSRIs, SNRIs, tricyclics, tryptophan
- Serotonin syndrome: hyperthermia, rigidity, myoclonus, death
- Meperidine or dextromethorphan
- Excitation, seizures, hyperpyrexia, coma
- Cold and cough medicines, nasal decongestants, amphetamines
- Hypertensive crisis
- Antihypertensives, including thiazides and beta-blockers
- Exaggerated fall in blood pressure
What is monitored
- Blood pressure frequently, including orthostatic
- Headache or palpitations (possible pressor reaction)
- Liver tests
- Mood and suicidal thoughts
Administration and safety
- Given by mouth; the medicine list is reviewed before any new drug, including over-the-counter cold remedies
- Other clinicians and dentists are told about phenelzine (local anaesthetics with vasoconstrictors, opioids)
- In a hypertensive crisis the drug is stopped at once; the label names phentolamine to lower blood pressure
- Switching to or from other antidepressants needs the waiting period on the label
Nursing care
- Teach the tyramine diet in detail, in writing, and that it continues for two weeks after the last dose
- Teach to report at once a severe headache, palpitations, neck stiffness or chest pain
- Check blood pressure lying and standing; fall precautions
- Teach to avoid over-the-counter cough, cold, decongestant and weight-loss products
- Assess suicidal thoughts early in treatment
Pregnancy and breastfeeding
Safe use in pregnancy has not been established; it is used only when the benefit outweighs the possible risk.
Test yourself
Think of the answer, then tap the question to see it.
A patient on phenelzine eats aged cheese and develops a sudden occipital headache, palpitations and severe hypertension. What happened?
A tyramine hypertensive crisis: with MAO blocked, dietary tyramine is not destroyed in the gut and liver and releases stored norepinephrine.
Why is meperidine contraindicated with phenelzine?
The combination can cause a serotonin-syndrome-like reaction with excitation, seizures, hyperpyrexia, circulatory collapse, coma and death.
For how long after the last dose does the phenelzine label keep the dietary restrictions?
Two weeks, because MAO activity takes time to recover after the drug is stopped.
Why is phenelzine rarely the first antidepressant chosen?
Because of the tyramine diet, the many dangerous drug interactions and the risk of hypertensive crisis; it is kept for depression that has not responded to other drugs.
Related drugs
← Back to the class: Monoamine oxidase inhibitors (MAOIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - PHENELZINE SULFATE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Phenelzine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2017); 2BXR: Human Monoamine Oxidase A in complex with Clorgyline, Crystal Form A (RCSB Protein Data Bank, 2005).
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Representative model, for educational purposes only.