Tranylcypromine (Parnate)

Tranylcypromine (Trade name: Parnate), also known as trans-2-phenylcyclopropylamine, is an antidepressant in the irreversible monoamine oxidase inhibitor (MAOI) class used in the treatment of major depressive disorder.

Pharmacokinetics of Tranylcypromine

Absorption Rapidly absorbed from the GI tract following oral administration. Peak plasma concentrations occur within 1 hour of dosing.
Distribution Distributed widely throughout the body.
Metabolism Liver; Phase I metabolism
Elimination Excreted in the urine, mainly in the form of metabolites
Half-life Although the half-life is only about 2 hours, the pharmacodynamic effects last several days to 1 week due to irreversible inhibition of MAO.[1]

Tranylcypromine: Cytochrome P450 Metabolism

Substrate of (Metabolized by) -
Induces -
Inhibits CYP 2A6
  • Monoamine oxidase (MAO) is the enzyme that degrades neurotransmitters including dopamine, norepinephrine, and serotonin.
    • MAO-A breaks down serotonin and norepinephrine and is found mainly in the gut.
    • MAO-B metabolizes phenylethylamine and is present in high concentrations in the basal ganglia and platelets
    • Both MAOA and MAOB break down dopamine
  • Tranylcypromine is mainly a non-hydrazine irreversible inhibitor of MAOA and is also an irreversible inhibitor of MAO-B but to a lesser degree.
  • Tranylcypromine thus increases levels of norepinephrine, epinephrine, serotonin, and dopamine.
    • Tranylcypromine is also structurally similar to amphetamine, which may contribute to stimulant-like effects.
  • At toxic doses, individuals can experience dizziness, sedation, insomnia, restlessness, headache, ataxia, cardiovascular effects, respiratory depression, or coma.

Dosing for Tranylcypromine

Starting 10 mg PO daily
Titration Increase by 10 mg every 1 to 3 weeks (may need to take in divided doses to manage side effects)
Maximum 60 mg PO daily
Taper Generally can taper within a few weeks (make sure to not overlap with other antidepressants for at least
  • Tranylcypromine comes in oral tablet formulation
  • Blood pressure should be monitored during treatment
  • Tranylcypromine increases the risk for a hypertensive crisis, especially if it interacts with other sympathomimetics.
  • Meperidine, fentanyl, guanethidine, dextromethorphan, buspirone, bupropion, sympathomimetic, or L- tryptophan.
  • Patients should not be on another MAOI currently or any medications that could inhibit serotonin reuptake, including SSRIs, sibutramine, tramadol, milnacipran, duloxetine, venlafaxine, clomipramine, and other serotonergic psychotropics.
  • Medical conditions including pheochromocytoma, cardiovascular or cerebrovascular disease, history of liver disease, or frequent or severe headaches.
  • Individuals with upcoming procedures or surgery that requires the administration of general anesthesia are sometimes recommended to discontinue MAOIs for 2 weeks the procedure.
  • Patients must be able to follow a low-tyramine diet.
  • Most SSRIs require 2 weeks of washout before starting an MAOI
    • Fluoxetine, however, because of its long half-life, requires a minimum of 5 weeks.[2]
  • Side effects are dose-related so some patients may require splitting the dose into 3 to 4 doses each day to manage these side effects
  • Common side effects include dry mouth, headaches, diarrhea, urinary hesitancy, insomnia, agitation, anxiety, nausea, and sexual dysfunction.
    • Postural hypotension, sometimes leading to syncope, is an important side effect to consider in the geriatric population
  • Increasing doses of tranylcypromine can increase supine blood pressure but not standing diastolic blood pressure.[3]
    • Note that this is separate from the tyramine-induced hypertensive crisis that can occur in MAOIs.
  • The risk of severe cerebrovascular events associated with hypertensive reactions has been estimated to be 1.4 to 7.0 per 100 000 individuals treated with tranylcypromine.[4]