View source for Tranylcypromine

{{Short description|Irreversible non-selective MAO inhibitor Antidepressant drug}}
{{Use dmy dates|date=March 2025}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 402690453
| image = Tranylcypromine stereoisomers labelled.svg
| image_class = skin-invert-image
| width = 300
| alt = 
| image2 = Tranylcypromine stereoisomers ball-and-stick models from xtal.png
| width2 = 300
| caption2 = (1''R'',2''S'')-(+)-tranylcypromine (left),<br/>(1''S'',2''R'')-(−)-tranylcypromine (right)

<!--Clinical data-->
| tradename = Parnate, many generics<ref name=generics/>
| Drugs.com = {{drugs.com|monograph|tranylcypromine-sulfate}}
| MedlinePlus = a682088
| DailyMedID = Tranylcypromine
| pregnancy_AU = B2
| pregnancy_category = 

| legal_AU = S4
| legal_AU_comment = <ref>https://www.tga.gov.au/resources/prescription-medicines-registrations/tranylcypromine-asp-medtas-pty-ltd</ref>
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| legal_status = Rx-only
| routes_of_administration = [[Oral administration|Oral]]

<!--Pharmacokinetic data-->
| bioavailability = 50%<ref name="Foye's">{{cite book | vauthors = Williams DA | chapter = Antidepressants | chapter-url = https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA590 | veditors = Foye WO, Lemke TL, Williams DA | title = Foye's Principles of Medicinal Chemistry | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, USA | year = 2007 | pages = 590–1 | isbn = 978-0-7817-6879-5}}</ref>
| metabolism = Liver<ref>{{Cite web|url=https://www.drugbank.ca/drugs/DB00752|title=Tranylcypromine|website=www.drugbank.ca|access-date=6 December 2019}}</ref><ref>{{cite journal | vauthors = Baker GB, Urichuk LJ, McKenna KF, Kennedy SH | title = Metabolism of monoamine oxidase inhibitors | journal = Cellular and Molecular Neurobiology | volume = 19 | issue = 3 | pages = 411–26 | date = June 1999 | pmid = 10319194 | doi = 10.1023/a:1006901900106 | s2cid = 21380176 | pmc = 11545467 }}</ref>
| elimination_half-life = 2.5 hours<ref name="Foye's"/>
| excretion = [[Urine]], [[Feces]]<ref name="Foye's"/>

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 155-09-9
| ATC_prefix = N06
| ATC_suffix = AF04
| PubChem = 19493
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00752
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 18369
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 9652
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 3E3V44J4Z9
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1179
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D08625
| synonyms = ''trans''-2-Phen<u>ylcy</u>clo<u>pro</u>pyla<u>mine</u>

<!--Chemical data-->
| IUPAC_name = (±)-''trans''-2-phenylcyclopropan-1-amine<br />or<br />''rel''-(1''R'',2''S'')-2-phenylcyclopropan-1-amine
| C=9 | H=11 | N=1
| SMILES = c1cccc(c1)[C@@H]2C[C@H]2N
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C9H11N/c10-9-6-8(9)7-4-2-1-3-5-7/h1-5,8-9H,6,10H2/t8-,9+/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AELCINSCMGFISI-DTWKUNHWSA-N
| chirality = [[Racemic mixture]]
}}

'''Tranylcypromine''', sold under the brand name '''Parnate''' among others,<ref name=generics>{{cite web | work = Drugs.com | url = https://www.drugs.com/international/tranylcypromine.html | title = International brands for Tranylcypromine | access-date = 17 April 2016 }}</ref> is a [[monoamine oxidase inhibitor]] (MAOI).<ref name="Foye's" /><ref name="G&G" /> More specifically, tranylcypromine acts as [[binding selectivity|nonselective]] and [[irreversible inhibition|irreversible]] [[enzyme inhibitor|inhibitor]] of the [[enzyme]] [[monoamine oxidase]] (MAO).<ref name="Foye's"/><ref name=G&G>{{cite book | vauthors = Baldessarini RJ |chapter=17. Drug therapy of depression and anxiety disorders |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics | veditors = Brunton LL, Lazo JS, Parker KL |year=2005 |isbn=978-0-07-142280-2 |location=New York |publisher=McGraw-Hill}}</ref> It is used as an [[antidepressant]] and [[anxiolytic]] agent in the [[clinic]]al [[therapy|treatment]] of [[mood disorder|mood]] and [[anxiety disorder]]s, respectively. It is also effective in the treatment of [[attention-deficit/hyperactivity disorder | ADHD]].<ref>Zametkin A, Rapoport JL, Murphy DL, Linnoila M, Ismond D. Treatment of hyperactive children with monoamine oxidase inhibitors. I. Clinical efficacy. Arch Gen Psychiatry. 1985 Oct;42(10):962-6. doi: 10.1001/archpsyc.1985.01790330042005. PMID: 3899047.</ref><ref>Levin GM. Attention-deficit hyperactivity disorder: the pharmacist's role. Am Pharm. 1995 Nov;NS35(11):10-20. PMID: 8533716.</ref>

Tranylcypromine is also known as ''trans''-2-phenylcyclopropyl-1-amine and is formed ''pro forma'' from the [[cyclization]] of [[amphetamine]]'s [[isopropylamine]] [[side chain]]. As a result, it is classified [[chemical structure|structurally]] as a [[substituted phenethylamine]] and [[substituted amphetamine|amphetamine]], or more specifically as a [[phenylcyclopropylamine]].

==Medical uses==
Tranylcypromine is used to treat [[major depressive disorder]], including [[atypical depression]], especially when there is an [[anxiety disorder|anxiety component]], typically as a second-line treatment.<ref name=EMC>{{cite web | work = UK Electronic medicines compendium. | url = https://www.medicines.org.uk/emc/medicine/25577 | title = Tranylcypromine | access-date = 28 October 2015 }}</ref> It is also used in depression that is not responsive to [[reuptake inhibitor]] antidepressants, such as the [[Selective serotonin reuptake inhibitor|SSRIs]], [[Tricyclic antidepressant|TCAs]], or [[bupropion]].<ref name="pmid22110357"/> In addition to being a recognized treatment for major depressive disorder, tranylcypromine has been demonstrated to be effective in treating
[[obsessive-compulsive disorder]]<ref>{{cite journal | vauthors = Jenike MA | title = Rapid response of severe obsessive-compulsive disorder to tranylcypromine | journal = The American Journal of Psychiatry | volume = 138 | issue = 9 | pages = 1249–1250 | date = September 1981 | pmid = 7270737 | doi = 10.1176/ajp.138.9.1249 }}</ref><ref>{{cite journal | vauthors = Marques C, Nardi AE, Mendlowicz M, Figueira I, Andrade Y, Camisão C, Coscarelli P, Versiani M | title = A tranilcipromina no tratamento do transtorno obsessivoðcompulsivo: relato de seis casos. | trans-title = The tranylcypromine in the treatment of obsessive-compulsive disorder: Report of six cases | language = pt-BR | journal = Jornal Brasileiro de Psiquiatria | date =  1994 | pages = 400–403 | url = https://www.researchgate.net/publication/294754327 }}</ref><ref>{{cite journal | vauthors = Joffe RT, Swinson RP | title=Tranylcypromine in primary obsessive-compulsive disorder | journal=Journal of Anxiety Disorders | volume=4 | issue=4 | date=1990 | doi=10.1016/0887-6185(90)90033-6 | pages=365–367 |url=https://psycnet.apa.org/record/1991-13396-001| url-access=subscription }}</ref> and [[panic disorder]].<ref>{{cite journal | vauthors = Nardi AE, Lopes FL, Valença AM, Freire RC, Nascimento I, Veras AB, Mezzasalma MA, de-Melo-Neto VL, Soares-Filho GL, King AL, Grivet LO, Rassi A, Versiani M | title = Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with panic disorder comorbid with social anxiety disorder | journal = Psychiatry Research | volume = 175 | issue = 3 | pages = 260–265 | date = February 2010 | pmid = 20036427 | doi = 10.1016/j.psychres.2008.06.025 | s2cid = 45566164 }}</ref><ref>{{cite journal | vauthors = Saeed SA, Bruce TJ | title = Panic disorder: effective treatment options | journal = American Family Physician | volume = 57 | issue = 10 | pages = 2405–2412 | date = May 1998 | pmid = 9614411 | url = https://www.aafp.org/pubs/afp/issues/1998/0515/p2405.html }}</ref>

[[Systematic review]]s and [[meta-analysis|meta-analyses]] have reported that tranylcypromine is significantly more effective in the treatment of depression than [[placebo]] and has efficacy over placebo similar to that of other antidepressants such as [[tricyclic antidepressant]]s.<ref name="pmid28579071">{{cite journal | vauthors = Ricken R, Ulrich S, Schlattmann P, Adli M | title = Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression | journal = Eur Neuropsychopharmacol | volume = 27 | issue = 8 | pages = 714–731 | date = August 2017 | pmid = 28579071 | doi = 10.1016/j.euroneuro.2017.04.003 | s2cid = 30987747 | url = | doi-access = free }}</ref><ref name="pmid31834088">{{cite journal | vauthors = Ulrich S, Ricken R, Buspavanich P, Schlattmann P, Adli M | title = Efficacy and Adverse Effects of Tranylcypromine and Tricyclic Antidepressants in the Treatment of Depression: A Systematic Review and Comprehensive Meta-analysis | journal = J Clin Psychopharmacol | volume = 40 | issue = 1 | pages = 63–74 | date = 2020 | pmid = 31834088 | doi = 10.1097/JCP.0000000000001153 | s2cid = 209343653 | url = }}</ref>

==Contraindications==
Contraindications include:<ref name=EMC/><ref name="pmid22110357"/><ref name="pmid21192146">{{cite journal | vauthors = Gillman PK | title = Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors | journal = Journal of Clinical Psychopharmacology | volume = 31 | issue = 1 | pages = 66–74 | date = February 2011 | pmid = 21192146 | doi = 10.1097/JCP.0b013e31820469ea | s2cid = 10525989 }}</ref>

* [[Porphyria]]
* [[Cardiovascular disease|Cardiovascular]] or [[cerebrovascular disease]]
* [[Pheochromocytoma]]
* [[Tyramine]], found in several foods, is metabolized by MAO. Ingestion and absorption of tyramine causes extensive release of [[norepinephrine]], which can rapidly increase blood pressure to the point of causing [[hypertensive crisis]].
* Concomitant use of serotonin-enhancing drugs, including [[Selective serotonin reuptake inhibitor|SSRIs]], serotonergic [[Tricyclic antidepressant|TCAs]], [[dextromethorphan]], and [[pethidine|meperidine]] may cause [[serotonin syndrome]].
* Concomitant use of [[Monoamine releasing agent|MRAs]], including [[fenfluramine]], [[amphetamine]], and [[pseudoephedrine]] may cause toxicity via serotonin syndrome or [[hypertensive crisis]].
* [[L-DOPA|<small>L</small>-DOPA]] given without [[carbidopa]] may cause hypertensive crisis.

===Dietary restrictions===
{{Main|Foods containing tyramine}}

[[Tyramine]] is a biogenic amine produced as a (generally undesirable) byproduct during the fermentation of certain tyrosine-rich foods. It is rapidly metabolized by [[Monoamine oxidase A|MAO-A]] in those not taking MAO-inhibiting drugs. Individuals sensitive to tyramine-induced hypertension may experience an uncomfortable, yet fleeting, increase in blood pressure after ingesting relatively small amounts of tyramine.<ref name="pmid28655495"/><ref name="pmid21192146"/><ref name = "Kim_2014">{{cite journal | doi=10.1016/j.lwt.2013.11.001 | title=Tyramine production among lactic acid bacteria and other species isolated from kimchi | year=2014 | vauthors = Kim MJ, Kim KS | journal=LWT - Food Science and Technology | volume=56 | issue=2 | pages=406–413 | doi-access=free }}</ref> 

Advances in food safety standards in most nations, as well as the widespread use of starter-cultures shown to result in undetectable to low levels of tyramine in fermented products has rendered concerns of serious hypertensive crises rare in those consuming a modern diet.<ref>{{cite journal | vauthors = Gillman PK | title = Monoamine oxidase inhibitors: a review concerning dietary tyramine and drug interactions. | journal = PsychoTropical Commentaries | date = 2016 | volume = 1 | pages = 1–90 | url = https://www.psychotropical.com/wp-content/uploads/4.20-MAOI_diet_long.pdf }}</ref><ref name = "Kim_2014" /> Those treated with MAOIs should still exercise caution, particularly at home, if it is unclear whether food has been properly refrigerated. Since tyramine-producing microbes also produce compounds to which humans have a natural aversion, disposal of any questionable food—particularly meats—should be sufficient to avoid hypertensive crises.

==Adverse effects==
'''<big>Incidence of adverse effects</big>'''<ref name="pmid28579071" />

'''Very common (>10% incidence) adverse effects include:'''
* Dizziness secondary to [[orthostatic hypotension]] (17%)

'''Common (1-10% incidence) adverse effects include:'''
* [[Tachycardia]] (5–10%)
* [[Hypomania]] (7%)
* [[Paresthesia]] (5%)
* Weight loss (2%)
* Confusion (2%)
* [[Xerostomia|Dry mouth]] (2%)
* Sexual function disorders (2%)
* [[Hypertension]] (1–2 hours after ingestion) (2%)
* Rash (2%)
* [[Urinary retention]] (2%)

'''Other (unknown incidence) adverse effects include:'''
* Increased/decreased appetite
* Blood dyscrasias
* Chest pain
* [[Diarrhea]]
* [[Edema]]
* [[Hallucination]]s
* [[Hyperreflexia]]
* [[Insomnia]]
* [[Jaundice]]
* Leg cramps
* [[Myalgia]]
* [[Palpitations]]
* Sensation of cold
* [[Suicidal ideation]]
* Tremor

Of note, there has not been found to be a correlation between sex and age below 65 regarding incidence of adverse effects.<ref name="pmid28579071"/>

Tranylcypromine is not associated with [[weight gain]] and has a low risk for hepatotoxicity compared to the [[hydrazine (Antidepressant)|hydrazine]] MAOIs.<ref name="pmid28579071"/><ref name="pmid22110357"/>

It is generally recommended that MAOIs be discontinued prior to [[anesthesia]]; however, this creates a risk of recurrent depression. In a retrospective observational cohort study, patients on tranylcypromine undergoing general anesthesia had a lower incidence of intraoperative hypotension, while there was no difference between patients not taking an MAOI regarding intraoperative incidence of [[bradycardia]], tachycardia, or hypertension.<ref>{{cite journal | vauthors = van Haelst IM, van Klei WA, Doodeman HJ, Kalkman CJ, Egberts TC | title = Antidepressive treatment with monoamine oxidase inhibitors and the occurrence of intraoperative hemodynamic events: a retrospective observational cohort study | journal = The Journal of Clinical Psychiatry | volume = 73 | issue = 8 | pages = 1103–9 | date = August 2012 | pmid = 22938842 | doi = 10.4088/JCP.11m07607 }}</ref> The use of indirect [[sympathomimetic drug]]s or drugs affecting serotonin reuptake, such as [[meperidine]] or [[dextromethorphan]] poses a risk for [[hypertension]] and [[serotonin syndrome]] respectively; alternative agents are recommended.<ref>{{cite journal | vauthors = Smith MS, Muir H, Hall R | title = Perioperative management of drug therapy, clinical considerations | journal = Drugs | volume = 51 | issue = 2 | pages = 238–59 | date = February 1996 | pmid = 8808166 | doi = 10.2165/00003495-199651020-00005 | s2cid = 46972638 }}</ref><ref>{{cite journal | vauthors = Blom-Peters L, Lamy M | title = Monoamine oxidase inhibitors and anesthesia: an updated literature review | journal = Acta Anaesthesiologica Belgica | volume = 44 | issue = 2 | pages = 57–60 | date = 1993 | pmid = 8237297 }}</ref> Other studies have come to similar conclusions.<ref name="pmid28579071"/> Pharmacokinetic interactions with anesthetics are unlikely, given that tranylcypromine is a high-affinity substrate for [[CYP2A6]] and does not inhibit CYP enzymes at therapeutic concentrations.<ref name="pmid28655495"/>

Tranylcypromine [[substance abuse|abuse]] has been reported at doses ranging from 120 to 600&nbsp;mg per day.<ref name=EMC/><ref>{{cite journal| vauthors = Le Gassicke J, Ashcroft GW, Eccleston D, Evans JI, Oswald I, Ritson EB |title=The Clinical State, Sleep and Amine Metabolism of a Tranylcypromine ('Parnate') Addict|journal=The British Journal of Psychiatry|date=1 April 1965|volume=111|issue=473|pages=357–364|doi=10.1192/bjp.111.473.357|s2cid=145562899 }}</ref><ref name="pmid28579071"/> It is thought that higher doses have more [[amphetamine]]-like effects and abuse is promoted by the fast onset and short half-life of tranylcypromine.<ref name="pmid28579071"/>

Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation.<ref name=EMC/>

Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.<ref name=EMC/>

==Interactions==
In addition to contraindicated concomitant medications, tranylcypromine inhibits [[CYP2A6]], which may reduce the metabolism and increase the toxicity of substrates of this enzyme, such as:<ref name="pmid21192146"/>

* [[Dexmedetomidine]]
* [[nicotine]]
* [[Tobacco-specific nitrosamines|TSNAs]] (found in cured tobacco products, including [[cigarette]]s)
* [[Valproate]]

[[Norepinephrine reuptake inhibitor]]s prevent neuronal uptake of [[tyramine]] and may reduce its [[pressor]] effects.<ref name="pmid21192146"/>

==Pharmacology==

===Pharmacodynamics===
Tranylcypromine acts as a nonselective and irreversible inhibitor of monoamine oxidase.<ref name="Foye's"/> Regarding the [[isoform]]s of monoamine oxidase, it shows slight preference for the [[MAO-B|MAOB]] [[isoenzyme]] over [[MAO-A|MAOA]].<ref name="pmid28655495"/> This leads to an increase in the availability of [[Monoamine neurotransmitter|monoamines]], such as [[serotonin]], [[norepinephrine]], and [[dopamine]], [[epinephrine]]  as well as a marked increase in the availability of [[trace amine]]s, such as [[tryptamine]], [[Octopamine (drug)|octopamine]], and [[phenethylamine]].<ref name="pmid28655495"/><ref name="pmid21192146"/> The clinical relevance of increased trace amine availability is unclear.

It may also act as a [[norepinephrine reuptake inhibitor]] at higher therapeutic doses.<ref name="pmid28655495"/> Compared to [[amphetamine]], tranylcypromine shows low potency as a [[dopamine]] [[releasing agent]], with even weaker potency for [[norepinephrine]] and [[serotonin]] release.<ref name="pmid28655495"/><ref name="pmid21192146"/>

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.<ref name="pmid16793513">{{cite journal | vauthors = Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R | title = Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications | journal = Chemistry & Biology | volume = 13 | issue = 6 | pages = 563–7 | date = June 2006 | pmid = 16793513 | doi = 10.1016/j.chembiol.2006.05.004 | doi-access =  }}</ref> The clinical relevance of this effect is unknown.

Tranylcypromine has been found to inhibit [[CYP46A1]] at nanomolar concentrations.<ref>{{cite journal | vauthors = Mast N, Charvet C, Pikuleva IA, Stout CD | title = Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain | journal = The Journal of Biological Chemistry | volume = 285 | issue = 41 | pages = 31783–95 | date = October 2010 | pmid = 20667828 | pmc = 2951250 | doi = 10.1074/jbc.M110.143313 | doi-access = free }}</ref> The clinical relevance of this effect is unknown.

[[File:Tranylcypromine-MAO-inhibiton.png|class=skin-invert-image|thumb|none|600px|Mechanism of tranylcypromine inhibition of MAO.<ref name="pmid22022344">{{cite journal | vauthors = Gaweska H, Fitzpatrick PF | title = Structures and Mechanism of the Monoamine Oxidase Family | journal = Biomolecular Concepts | volume = 2 | issue = 5 | pages = 365–377 | date = October 2011 | pmid = 22022344 | pmc = 3197729 | doi = 10.1515/BMC.2011.030 }}</ref>]]

===Pharmacokinetics===
Tranylcypromine reaches its maximum concentration (t<sub>max</sub>) within 1–2 hours.<ref name="pmid28655495">{{cite journal | vauthors = Ulrich S, Ricken R, Adli M | title = Tranylcypromine in mind (Part I): Review of pharmacology | journal = European Neuropsychopharmacology | volume = 27 | issue = 8 | pages = 697–713 | date = August 2017 | pmid = 28655495 | doi = 10.1016/j.euroneuro.2017.05.007 | s2cid = 4913721 | doi-access = free }}</ref> After a 20&nbsp;mg dose, plasma concentrations reach at most 50-200&nbsp;ng/mL.<ref name="pmid28655495"/> While its [[Biological half-life|half-life]] is only about 2 hours, its pharmacodynamic effects last several days to weeks due to irreversible inhibition of MAO.<ref name="pmid28655495"/>

Metabolites of tranylcypromine include 4-hydroxytranylcypromine, ''N''-acetyltranylcypromine, and ''N''-acetyl-4-hydroxytranylcypromine, which are less potent MAO inhibitors than tranylcypromine itself.<ref name="pmid28655495"/> [[Amphetamine]] was once thought to be a metabolite of tranylcypromine, but has not been shown to be.<ref name="pmid28655495"/><ref>{{cite journal | vauthors = Sherry RL, Rauw G, McKenna KF, Paetsch PR, Coutts RT, Baker GB | title = Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine | journal = Journal of Affective Disorders | volume = 61 | issue = 1–2 | pages = 23–9 | date = December 2000 | pmid = 11099737 | doi = 10.1016/s0165-0327(99)00188-3 }}</ref><ref name="pmid21192146"/>

Tranylcypromine inhibits [[CYP2A6]] at therapeutic concentrations.<ref name="pmid21192146"/>

==Chemistry==
<gallery mode=packed heights=180px>
Tranylcypromine-10mg-Quarter.jpg|Tranylcypromine 10-mg tablet
Tranylcypromine India.jpg|A box of tranylcypromine manufactured in [[India]]
</gallery>

===Synthesis===
[[File:Tranylcypromine-synth.png|class=skin-invert-image|thumb|none|1000px|Synthesis of tranylcypromine<ref>{{cite patent|country=US|number=4016204 A|status=patent|title=Method of synthesis of trans-2-phenylcyclopropylamine |pubdate=1977-04-05 |fdate=1975-10-31 |pridate=1975-10-31 |inventor= Rajadhyaksha VJ |assign1=Nelson Research & Development Company }}</ref>]]

==History==
Tranylcypromine was originally developed as an [[analog (chemistry)|analog]] of [[amphetamine]].<ref name="Foye's"/><ref name="pmid28655495"/> Although it was first synthesized in 1948,<ref>{{cite journal| vauthors = Burger A, Yost WL |title=Arylcycloalkylamines. I. 2-Phenylcyclopropylamine|journal=Journal of the American Chemical Society|volume=70|issue=6|pages=2198–2201|doi=10.1021/ja01186a062|year=1948|bibcode=1948JAChS..70.2198B }}</ref> 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.<ref>{{cite journal | vauthors = López-Muñoz F, Alamo C | title = Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today | journal = Current Pharmaceutical Design | volume = 15 | issue = 14 | pages = 1563–86 | date = 2009 | pmid = 19442174 | doi = 10.2174/138161209788168001 }}</ref>

The drug was introduced by [[Smith, Kline and French]] in the [[United Kingdom]] in 1960, and approved in the [[United States]] in 1961.<ref name="isbn0-19-536874-6">{{cite book | vauthors = Shorter E | title = Before Prozac: the troubled history of mood disorders in psychiatry | publisher = Oxford University Press | location = Oxford [Oxfordshire] | year = 2009 | isbn = 978-0-19-536874-1 | url = https://books.google.com/books?id=8VaYF8pIPxgC&pg=PR13}}</ref> 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.<ref>{{cite journal | vauthors = Atchley DW | title = Reevaluation of Tranylcypromine Sulfate(Parnate Sulfate) | journal = JAMA | volume = 189 | issue = 10 | pages = 763–4 | date = September 1964 | pmid = 14174054 | doi = 10.1001/jama.1964.03070100057011 }}</ref><ref name="pmid28655495"/><ref name="pmid21192146"/>

==Research==
Tranylcypromine is known to inhibit [[KDM1A|LSD1]], an enzyme that selectively [[Methyl group|demethylates]] two [[lysine]]s found on [[histone H3]].<ref name="pmid16793513"/><ref name="pmid28655495"/><ref name="pmid26881714">{{cite journal | vauthors = Zheng YC, Yu B, Jiang GZ, Feng XJ, He PX, Chu XY, Zhao W, Liu HM | title = Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment | journal = Current Topics in Medicinal Chemistry | volume = 16 | issue = 19 | pages = 2179–88 | date = 2016 | pmid = 26881714 | doi = 10.2174/1568026616666160216154042 }}</ref> Genes promoted downstream of LSD1 are involved in cancer cell growth and metastasis, and several tumor cells express high levels of LSD1.<ref name="pmid26881714"/> Tranylcypromine analogues with more potent and selective LSD1 inhibitory activity are being researched in the potential treatment of cancers.<ref name="pmid26881714"/><ref name="pmid27077938">{{cite journal | vauthors = Przespolewski A, Wang ES | title = Inhibitors of LSD1 as a potential therapy for acute myeloid leukemia | journal = Expert Opinion on Investigational Drugs | volume = 25 | issue = 7 | pages = 771–80 | date = July 2016 | pmid = 27077938 | doi = 10.1080/13543784.2016.1175432 | s2cid = 20858344 }}</ref>

Tranylcypromine may have neuroprotective properties applicable to the treatment of [[Parkinson's disease]], similar to the [[Monoamine oxidase B|MAO-B]] inhibitors [[selegiline]] and [[rasagiline]].<ref name="pmid22960850">{{cite journal | vauthors = Al-Nuaimi SK, Mackenzie EM, Baker GB | title = Monoamine oxidase inhibitors and neuroprotection: a review | journal = American Journal of Therapeutics | volume = 19 | issue = 6 | pages = 436–48 | date = November 2012 | pmid = 22960850 | doi = 10.1097/MJT.0b013e31825b9eb5 }}</ref><ref name="pmid22110357">{{cite journal | vauthors = Riederer P, Laux G | title = MAO-inhibitors in Parkinson's Disease | journal = Experimental Neurobiology | volume = 20 | issue = 1 | pages = 1–17 | date = March 2011 | pmid = 22110357 | pmc = 3213739 | doi = 10.5607/en.2011.20.1.1 }}</ref> As of 2017, only one clinical trial in Parkinsonian patients has been conducted, which found some improvement initially and only slight worsening of symptoms after a 1.5 year followup.<ref name="pmid22110357"/>

==See also==
* [[Tranylcypromine/trifluoperazine]]
*[[Cyprolidol]]
==References==
{{Reflist}}

{{Antidepressants}}
{{Monoamine metabolism modulators}}
{{Prostanoid signaling modulators}}
{{Phenethylamines}}
{{GlaxoSmithKline}}

[[Category:CYP2A6 inhibitors]]
[[Category:CYP2D6 inhibitors]]
[[Category:CYP46A1 inhibitors]]
[[Category:Monoamine oxidase inhibitors]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Phenylcyclopropylamines]]
[[Category:Substituted amphetamines]]
[[Category:Substances discovered in the 1940s]]