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ApprovedFDA approvedStrong evidence

Tranylcypromine

Irreversible, non-selective MAO inhibitor antidepressant for treatment-resistant depression.

AntidepressantMAOIAntidepressantMoodSerotoninNorepinephrineDopamine

Pharmacology

ClassAntidepressant · Mood
Primary targetMAO-A irreversible inhibition
Targets3 receptor targets
Half-lifePlasma half-life about 1.5-3.5 hours, but the effect lasts 1-2 weeks due to irreversible enzyme inhibition
OnsetMood effect builds over 2-6 weeks
EvidenceStrong evidence
Affected systemsSerotoninNorepinephrineDopamine

Contents

WHAT IS TRANYLCYPROMINE?

Detailed overview

Tranylcypromine (Parnate) is an irreversible, non-selective monoamine oxidase (MAO) inhibitor used mainly for treatment-resistant major depression after other antidepressants have failed. Its cyclopropylamine scaffold is amphetamine-like, so alongside sustained blockade of MAO-A and MAO-B it adds mild stimulant and norepinephrine-reuptake-inhibiting activity, raising serotonin, noradrenaline and dopamine together. The clinical effect builds over several weeks, and because the enzyme inhibition is irreversible, the effect persists 1-2 weeks after the drug itself has cleared. It is a potent, long-approved medicine that must be used only with a strict low-tyramine diet and careful attention to drug interactions.

Mechanism

Irreversible, non-selective MAO-A/B inhibitor

Onset

Several weeks; enzyme block lasts 1-2 weeks

Legal status

Prescription antidepressant (FDA/EMA)

Receptor profile

  • MAO-A enzyme (irreversible)Strong
  • MAO-B enzyme (irreversible)Strong
  • Monoamine release / reuptake (amphetamine-like, weak)Weak

Safety

Side effects, stop signs, contraindications

Side effects · 5

  • Orthostatic hypotension: dizziness, lightheadedness on standing, the most common dose-limiting complaint
  • Insomnia and restlessness, especially with late-afternoon dosing (mild stimulant effect)
  • Hypertensive crisis risk with tyramine-rich foods (aged cheese, cured meat, beer): severe headache, spiking blood pressure
  • Serotonin syndrome risk when combined with SSRIs, SNRIs, triptans or other serotonergic agents
  • Weight change, sexual dysfunction, dry mouth

Contraindications · 5

  • Concurrent SSRIs/SNRIs/tricyclics or other MAO inhibitors: serotonin syndrome, a washout period is required
  • Failure to follow a low-tyramine diet: hypertensive crisis, so strict dietary restriction is required
  • Sympathomimetics (pseudoephedrine, amphetamines), cold remedies: blood-pressure crisis
  • Pheochromocytoma, severe cardiovascular disease, cerebrovascular disease
  • Pregnancy and breastfeeding: only after clear benefit-risk assessment under medical supervision

Related Nootropics

Same therapeutic category

Studies

Related research and clinical findings

FAQ

FAQ

Irreversible, non-selective MAO inhibitor antidepressant for treatment-resistant depression.

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Structure & chemistry

TypeAntidepressant
FormulaC9H11N
UpdatedJuly 10, 2026
MolekulaX Editorial Team·Source-verified · PubMed · FDA · EMA
Updated: July 10, 2026

The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.