People taking other MAOis, sympathomimetic amines such as amphetamine, fenfluramine or similar anti-obesity agents, ephedrine, levodopa or dopamine, pethidine and closely related narcotic analgesics, nefopam, dextromethorphan, or buspirone
The most common side effect of tranylcypromine is insomnia; other side effects include orthostatic or postural hypotension, dizziness, drowsiness, fatigue, dry mouth, blurred vision, headache, diarrhoea, nausea and vomiting, sleep disturbances, rash and rarely hepatocellular damage, jaundice, hallucinations and blood dyscrasias. Overstimulation including anxiety and agitation, developing rarely into hypomanias; severe hypertensive reactions may occur.
At least one case of the abuse of tranylcypromine has been noted.
Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation.
Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.
Tranylcypromine has also been shown to inhibit the histone demethylase, BHC110/LSD1. Tranylcypromine inhibits this enzyme with an IC50 < 2 µM, thus acting as a small molecule inhibitor of histone demethylation with an effect to derepress the transcriptional activity of BHC110/LSD1 target genes.
Tranylcypromine was originally developed as an analog of amphetamine. Although it was first synthesized in 1948, its MAOI action was not discovered until 1959. Precisely because tranylcypromine was not, like isoniazid and iproniazid, a hydrazine derivative, its clinical interest increased enormously, as it was thought it might have a more acceptable therapeutic index than previous MAOIs.
The drug was introduced by Smith, Kline and French in the United Kingdom in 1960, and approved in the United States in 1961. It was withdrawn from the market in February 1964 due to a number of patient deaths involving hypertensive crises with intracranial bleeding. However, it was reintroduced later that year with more limited indications and specific warnings of the risks.
^ abcdefWilliams, David A. (2007). "Antidepressants". In Foye, William O.; Lemke, Thomas L.; Williams, David A. Foye's Principles of Medicinal Chemistry. Hagerstwon, USA: Lippincott Williams & Wilkins. pp. 590–1. ISBN0-7817-6879-9.
^ abBaldessarini, Ross J. (2005). "17. Drug therapy of depression and anxiety disorders". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. ISBN0-07-142280-3.
^Le Gassicke, J; Ashcroft, GW; Eccleston, D; Evans, JI; Oswald, I; Ritson, EB (1 April 1965). "The Clinical State, Sleep and Amine Metabolism of a Tranylcypromine (`Parnate') Addict". The British Journal of Psychiatry111 (473): 357–364. doi:10.1192/bjp.111.473.357.
^Lee, MG; Wynder, C; Schmidt, DM; McCafferty, DG; Shiekhattar, R (June 2006). "Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications.". Chemistry & Biology13 (6): 563–7. doi:10.1016/j.chembiol.2006.05.004. PMID16793513.
^Burger, A; Yost, WL. "Arylcycloalkylamines. I. 2-Phenylcyclopropylamine". Journal of the American Chemical Society70 (6): 2198–2201. doi:10.1021/ja01186a062.
^López-Muñoz, F; Alamo, C (2009). "Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today.". Current Pharmaceutical Design15 (14): 1563–86. doi:10.2174/138161209788168001. PMID19442174.