Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant for treatment resistant major depressive disorder and atypical depression and functions by forming a covalent adduct with the flavin adenine dinucleotide prosthetic group of MAO, thereby preventing oxidative deamination of monoamine neurotransmitters including serotonin, norepinephrine and dopamine and increasing their synaptic availability. Chemically identified as trans-2-phenylcyclopropylamine, tranylcypromine is a small, lipophilic primary amine that crosses the blood brain barrier, is subject to hepatic metabolism and conjugation, and produces effectively irreversible enzyme inhibition until new MAO protein is synthesized; clinical dosing requires titration and monitoring for hypertensive reactions with dietary tyramine exposure and for serotonergic toxicity when combined with other monoamine-active agents.
Parent: Tranylcypromine
Parent: Tranylcypromine
Parent: Tranylcypromine
Parent: Tranylcypromine
Typical quality control specifications for tranylcypromine drug substance include assay by validated HPLC 98.0 to 102.0 percent on an anhydrous basis, total related substances not greater than 0.50 percent area by HPLC and any individual unspecified impurity not greater than 0.10 percent area; specified related compounds and acceptance criteria commonly applied are cis-2-phenylcyclopropylamine (stereoisomer) up to 0.20 percent, relevant N-oxide impurities up to 0.20 percent and identified ring-opened or deaminated degradants limited to 0.10 percent each. Control of inorganic and process residuals is required, for example heavy metals typically limited to 20 ppm and residual solvents controlled per ICH Q3C with limits such as methanol 3000 ppm and dichloromethane 600 ppm when applicable. Analytical characterization employs chiral HPLC for stereoisomer content, reversed-phase HPLC-UV or HPLC-MS for related substances, GC-MS for residual solvents and ICP for elemental impurities, and stability studies under ICH conditions are used to define storage conditions and shelf-life based on impurity/profile evolution.
Tranylcypromine should not be given with serotonergic agents such as SSRIs, SNRIs, tricyclic antidepressants, bupropion and certain opioid analgesics like meperidine and tramadol because of the risk of serotonin syndrome and severe interactions. It is contraindicated with other MAO inhibitors and with linezolid and methylene blue because of hypertensive and serotonergic risks. Sympathomimetic agents including pseudoephedrine and phenylpropanolamine, certain anesthetic agents and herbal serotonergic products such as St John’s wort are also contraindicated or require strict management. Washout periods are required when switching from many antidepressants, for example at least 2 weeks from most SSRIs and longer from fluoxetine.
Tranylcypromine is nonselective and inhibits both MAO-A and MAO-B irreversibly, so it does not act selectively as MAO-A or MAO-B inhibitor.
Tranylcypromine differs mechanistically by producing irreversible, nonselective inhibition of MAO leading to broad increases in monoamines rather than selectively blocking reuptake of a single transmitter as SSRIs or SNRIs do; clinically this means it can be effective in treatment resistant and atypical depression but requires dietary tyramine precautions and has a higher risk of severe drug interactions and hypertensive crises, and its side effect and safety profile and switching requirements therefore differ substantially from reversible or selective antidepressants.
