Tranylcypromine: Difference between revisions

Tranylcypromine
	(1S,2R)-(−)-tranylcypromine (top),; (1R,2S)-(+)-tranylcypromine (bottom)
Clinical data
Trade names	Parnate, many generics
Other names	trans-2-Phenylcyclopropylamine
AHFS/Drugs.com	Monograph
MedlinePlus	a682088
Pregnancy; category	AU: B2; ;
Routes of; administration	Oral
ATC code	N06AF04 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); BR: Class C1 (Other controlled substances); CA: ℞-only; UK: POM (Prescription only); US: WARNINGRx-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	50%
Metabolism	Liver
Elimination half-life	2.5 hours
Excretion	Urine, Feces
Identifiers
	IUPAC name (±)-trans-2-phenylcyclopropan-1-amine; or; rel-(1R,2S)-2-phenylcyclopropan-1-amine;
CAS Number	155-09-9 ;
PubChem CID	19493;
DrugBank	DB00752 ;
ChemSpider	18369 ;
UNII	3E3V44J4Z9;
KEGG	D08625 ;
ChEBI	CHEBI:9652 ;
ChEMBL	ChEMBL1179 ;
ECHA InfoCard	100.005.312
Chemical and physical data
Formula	C9H11N
Molar mass	133.194 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES c1cccc(c1)[C@@H]2C[C@H]2N;
	InChI InChI=1S/C9H11N/c10-9-6-8(9)7-4-2-1-3-5-7/h1-5,8-9H,6,10H2/t8-,9+/m0/s1 ; Key:AELCINSCMGFISI-DTWKUNHWSA-N ;
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Latest revision as of 06:17, 2 September 2024

Tranylcypromine, sold under the brand name Parnate among others,^[1] is a monoamine oxidase inhibitor (MAOI).^[4]^[7] More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO).^[4]^[7] It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. It is also effective in the treatment of ADHD.^[8]^[9]

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 structurally as a substituted phenethylamine and amphetamine.

Medical uses

Tranylcypromine is used to treat major depressive disorder, including atypical depression, especially when there is an anxiety component, typically as a second-line treatment.^[10] It is also used in depression that is not responsive to reuptake inhibitor antidepressants, such as the SSRIs, TCAs, or bupropion.^[11] In addition to being a recognized treatment for major depressive disorder, tranylcypromine has been demonstrated to be effective in treating obsessive compulsive disorder^[12]^[13]^[14] and panic disorder.^[15]^[16]

Systematic reviews and 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 antidepressants.^[17]^[18]

Contraindications

Contraindications include:^[10]^[11]^[19]

Porphyria
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 SSRIs, serotonergic TCAs, dextromethorphan, and meperidine may cause serotonin syndrome.
Concomitant use of MRAs, including fenfluramine, amphetamine, and pseudoephedrine may cause toxicity via serotonin syndrome or hypertensive crisis.
L-DOPA given without carbidopa may cause hypertensive crisis.

Dietary restrictions

Tyramine is a biogenic amine produced as a (generally undesirable) byproduct during the fermentation of certain tyrosine-rich foods. It is rapidly metabolized by 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. ^[20]^[19]^[21]

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.^[22]^[21] 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

Incidence of adverse effects^[17]

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%)
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
Hallucinations
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.^[17]

Tranylcypromine is not associated with weight gain and has a low risk for hepatotoxicity compared to the hydrazine MAOIs.^[17]^[11]

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.^[23] The use of indirect sympathomimetic drugs or drugs affecting serotonin reuptake, such as meperidine or dextromethorphan poses a risk for hypertension and serotonin syndrome respectively; alternative agents are recommended.^[24]^[25] Other studies have come to similar conclusions.^[17] 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.^[20]

Tranylcypromine abuse has been reported at doses ranging from 120 to 600 mg per day.^[10]^[26]^[17] 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.^[17]

Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation.^[10]

Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.^[10]

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:^[19]

Dexmedetomidine
nicotine
TSNAs (found in cured tobacco products, including cigarettes)
Valproate

Norepinephrine reuptake inhibitors prevent neuronal uptake of tyramine and may reduce its pressor effects.^[19]

Pharmacology

Pharmacodynamics

Tranylcypromine acts as a nonselective and irreversible inhibitor of monoamine oxidase.^[4] Regarding the isoforms of monoamine oxidase, it shows slight preference for the MAOB isoenzyme over MAOA.^[20] This leads to an increase in the availability of monoamines, such as serotonin, norepinephrine, and dopamine, epinephrine as well as a marked increase in the availability of trace amines, such as tryptamine, octopamine, and phenethylamine.^[20]^[19] The clinical relevance of increased trace amine availability is unclear.

It may also act as a norepinephrine reuptake inhibitor at higher therapeutic doses.^[20] Compared to amphetamine, tranylcypromine shows low potency as a dopamine releasing agent, with even weaker potency for norepinephrine and serotonin release.^[20]^[19]

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.^[27] The clinical relevance of this effect is unknown.

Tranylcypromine has been found to inhibit CYP46A1 at nanomolar concentrations.^[28] The clinical relevance of this effect is unknown.

Mechanism of tranylcypromine inhibition of MAO.^[29]

Pharmacokinetics

Tranylcypromine reaches its maximum concentration (t_max) within 1–2 hours.^[20] After a 20 mg dose, plasma concentrations reach at most 50-200 ng/mL.^[20] While its half-life is only about 2 hours, its pharmacodynamic effects last several days to weeks due to irreversible inhibition of MAO.^[20]

Metabolites of tranylcypromine include 4-hydroxytranylcypromine, N-acetyltranylcypromine, and N-acetyl-4-hydroxytranylcypromine, which are less potent MAO inhibitors than tranylcypromine itself.^[20] Amphetamine was once thought to be a metabolite of tranylcypromine, but has not been shown to be.^[20]^[30]^[19]

Tranylcypromine inhibits CYP2A6 at therapeutic concentrations.^[19]

Chemistry

Synthesis

History

Tranylcypromine was originally developed as an analog of amphetamine.^[4]^[20] Although it was first synthesized in 1948,^[32] 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.^[33]

The drug was introduced by Smith, Kline and French in the United Kingdom in 1960, and approved in the United States in 1961.^[34] 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.^[35]^[20]^[19]

Research

Tranylcypromine is known to inhibit LSD1, an enzyme that selectively demethylates two lysines found on histone H3.^[27]^[20]^[36] Genes promoted downstream of LSD1 are involved in cancer cell growth and metastasis, and several tumor cells express high levels of LSD1.^[36] Tranylcypromine analogues with more potent and selective LSD1 inhibitory activity are being researched in the potential treatment of cancers.^[36]^[37]

Tranylcypromine may have neuroprotective properties applicable to the treatment of Parkinson's disease, similar to the MAO-B inhibitors selegiline and rasagiline.^[38]^[11] 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.^[11]

References

^ ^a ^b "International brands for Tranylcypromine". Drugs.com. Retrieved 17 April 2016.
^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ ^a ^b ^c ^d ^e ^f ^g Williams DA (2007). "Antidepressants". In Foye WO, Lemke TL, Williams DA (eds.). Foye's Principles of Medicinal Chemistry. Hagerstwon, USA: Lippincott Williams & Wilkins. pp. 590–1. ISBN 978-0-7817-6879-5.
^ "Tranylcypromine". www.drugbank.ca. Retrieved 2019-12-06.
^ Baker GB, Urichuk LJ, McKenna KF, Kennedy SH (June 1999). "Metabolism of monoamine oxidase inhibitors". Cellular and Molecular Neurobiology. 19 (3): 411–26. doi:10.1023/a:1006901900106. PMID 10319194. S2CID 21380176.
^ ^a ^b Baldessarini RJ (2005). "17. Drug therapy of depression and anxiety disorders". In Brunton LL, Lazo JS, Parker KL (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. ISBN 978-0-07-142280-2.
^ 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.
^ Levin GM. Attention-deficit hyperactivity disorder: the pharmacist's role. Am Pharm. 1995 Nov;NS35(11):10-20. PMID: 8533716.
^ ^a ^b ^c ^d ^e "Tranylcypromine". UK Electronic medicines compendium. Retrieved 28 October 2015.
^ ^a ^b ^c ^d ^e Riederer P, Laux G (March 2011). "MAO-inhibitors in Parkinson's Disease". Experimental Neurobiology. 20 (1): 1–17. doi:10.5607/en.2011.20.1.1. PMC 3213739. PMID 22110357.
^ Jenike MA (September 1981). "Rapid response of severe obsessive-compulsive disorder to tranylcypromine". The American Journal of Psychiatry. 138 (9): 1249–1250. doi:10.1176/ajp.138.9.1249. PMID 7270737.
^ Marques C, Nardi AE, Mendlowicz M, Figueira I, Andrade Y, Camisão C, et al. (1994). "A tranilcipromina no tratamento do transtorno obsessivoðcompulsivo: relato de seis casos" [The tranylcypromine in the treatment of obsessive-compulsive disorder: Report of six cases]. Jornal Brasileiro de Psiquiatria (in Brazilian Portuguese). pp. 400–403.
^ Joffe RT, Swinson RP (1990). "Tranylcypromine in primary obsessive-compulsive disorder". Journal of Anxiety Disorders. 4 (4): 365–367. doi:10.1016/0887-6185(90)90033-6.
^ Nardi AE, Lopes FL, Valença AM, Freire RC, Nascimento I, Veras AB, et al. (February 2010). "Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with panic disorder comorbid with social anxiety disorder". Psychiatry Research. 175 (3): 260–265. doi:10.1016/j.psychres.2008.06.025. PMID 20036427. S2CID 45566164.
^ Saeed SA, Bruce TJ (May 1998). "Panic disorder: effective treatment options". American Family Physician. 57 (10): 2405–2412. PMID 9614411.
^ ^a ^b ^c ^d ^e ^f ^g Ricken R, Ulrich S, Schlattmann P, Adli M (August 2017). "Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression". Eur Neuropsychopharmacol. 27 (8): 714–731. doi:10.1016/j.euroneuro.2017.04.003. PMID 28579071. S2CID 30987747.
^ Ulrich S, Ricken R, Buspavanich P, Schlattmann P, Adli M (2020). "Efficacy and Adverse Effects of Tranylcypromine and Tricyclic Antidepressants in the Treatment of Depression: A Systematic Review and Comprehensive Meta-analysis". J Clin Psychopharmacol. 40 (1): 63–74. doi:10.1097/JCP.0000000000001153. PMID 31834088. S2CID 209343653.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Gillman PK (February 2011). "Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors". Journal of Clinical Psychopharmacology. 31 (1): 66–74. doi:10.1097/JCP.0b013e31820469ea. PMID 21192146. S2CID 10525989.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ Ulrich S, Ricken R, Adli M (August 2017). "Tranylcypromine in mind (Part I): Review of pharmacology". European Neuropsychopharmacology. 27 (8): 697–713. doi:10.1016/j.euroneuro.2017.05.007. PMID 28655495. S2CID 4913721.
^ ^a ^b Kim MJ, Kim KS (2014). "Tyramine production among lactic acid bacteria and other species isolated from kimchi". LWT - Food Science and Technology. 56 (2): 406–413. doi:10.1016/j.lwt.2013.11.001.
^ Gillman PK (2016). "Monoamine oxidase inhibitors: a review concerning dietary tyramine and drug interactions" (PDF). PsychoTropical Commentaries. 1: 1–90.
^ van Haelst IM, van Klei WA, Doodeman HJ, Kalkman CJ, Egberts TC (August 2012). "Antidepressive treatment with monoamine oxidase inhibitors and the occurrence of intraoperative hemodynamic events: a retrospective observational cohort study". The Journal of Clinical Psychiatry. 73 (8): 1103–9. doi:10.4088/JCP.11m07607. PMID 22938842.
^ Smith MS, Muir H, Hall R (February 1996). "Perioperative management of drug therapy, clinical considerations". Drugs. 51 (2): 238–59. doi:10.2165/00003495-199651020-00005. PMID 8808166. S2CID 46972638.
^ Blom-Peters L, Lamy M (1993). "Monoamine oxidase inhibitors and anesthesia: an updated literature review". Acta Anaesthesiologica Belgica. 44 (2): 57–60. PMID 8237297.
^ 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 Psychiatry. 111 (473): 357–364. doi:10.1192/bjp.111.473.357. S2CID 145562899.
^ ^a ^b 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 & Biology. 13 (6): 563–7. doi:10.1016/j.chembiol.2006.05.004. PMID 16793513.
^ Mast N, Charvet C, Pikuleva IA, Stout CD (October 2010). "Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain". The Journal of Biological Chemistry. 285 (41): 31783–95. doi:10.1074/jbc.M110.143313. PMC 2951250. PMID 20667828.
^ Gaweska H, Fitzpatrick PF (October 2011). "Structures and Mechanism of the Monoamine Oxidase Family". Biomolecular Concepts. 2 (5): 365–377. doi:10.1515/BMC.2011.030. PMC 3197729. PMID 22022344.
^ Sherry RL, Rauw G, McKenna KF, Paetsch PR, Coutts RT, Baker GB (December 2000). "Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine". Journal of Affective Disorders. 61 (1–2): 23–9. doi:10.1016/s0165-0327(99)00188-3. PMID 11099737.
^ A US patent 4016204 A, Rajadhyaksha VJ, "Method of synthesis of trans-2-phenylcyclopropylamine", published 1977-04-05, assigned to Nelson Research & Development Company
^ Burger A, Yost WL (1948). "Arylcycloalkylamines. I. 2-Phenylcyclopropylamine". Journal of the American Chemical Society. 70 (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 Design. 15 (14): 1563–86. doi:10.2174/138161209788168001. PMID 19442174.
^ Shorter E (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-536874-1.
^ Atchley DW (September 1964). "Reevaluation of Tranylcypromine Sulfate(Parnate Sulfate)". JAMA. 189 (10): 763–4. doi:10.1001/jama.1964.03070100057011. PMID 14174054.
^ ^a ^b ^c Zheng YC, Yu B, Jiang GZ, Feng XJ, He PX, Chu XY, et al. (2016). "Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment". Current Topics in Medicinal Chemistry. 16 (19): 2179–88. doi:10.2174/1568026616666160216154042. PMID 26881714.
^ Przespolewski A, Wang ES (July 2016). "Inhibitors of LSD1 as a potential therapy for acute myeloid leukemia". Expert Opinion on Investigational Drugs. 25 (7): 771–80. doi:10.1080/13543784.2016.1175432. PMID 27077938. S2CID 20858344.
^ Al-Nuaimi SK, Mackenzie EM, Baker GB (November 2012). "Monoamine oxidase inhibitors and neuroprotection: a review". American Journal of Therapeutics. 19 (6): 436–48. doi:10.1097/MJT.0b013e31825b9eb5. PMID 22960850.

[generics-1] "International brands for Tranylcypromine". Drugs.com. Retrieved 17 April 2016.

[FDA-AllBoxedWarnings-2] "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.

[3] Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.

[Foye's-4] ^ ^a ^b ^c ^d ^e ^f ^g Williams DA (2007). "Antidepressants". In Foye WO, Lemke TL, Williams DA (eds.). Foye's Principles of Medicinal Chemistry. Hagerstwon, USA: Lippincott Williams & Wilkins. pp. 590–1. ISBN 978-0-7817-6879-5.

[5] "Tranylcypromine". www.drugbank.ca. Retrieved 2019-12-06.

[6] Baker GB, Urichuk LJ, McKenna KF, Kennedy SH (June 1999). "Metabolism of monoamine oxidase inhibitors". Cellular and Molecular Neurobiology. 19 (3): 411–26. doi:10.1023/a:1006901900106. PMID 10319194. S2CID 21380176.

[G&G-7] Baldessarini RJ (2005). "17. Drug therapy of depression and anxiety disorders". In Brunton LL, Lazo JS, Parker KL (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. ISBN 978-0-07-142280-2.

[8] 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.

[9] Levin GM. Attention-deficit hyperactivity disorder: the pharmacist's role. Am Pharm. 1995 Nov;NS35(11):10-20. PMID: 8533716.

[EMC-10] "Tranylcypromine". UK Electronic medicines compendium. Retrieved 28 October 2015.

[pmid22110357-11] Riederer P, Laux G (March 2011). "MAO-inhibitors in Parkinson's Disease". Experimental Neurobiology. 20 (1): 1–17. doi:10.5607/en.2011.20.1.1. PMC 3213739. PMID 22110357.

[12] Jenike MA (September 1981). "Rapid response of severe obsessive-compulsive disorder to tranylcypromine". The American Journal of Psychiatry. 138 (9): 1249–1250. doi:10.1176/ajp.138.9.1249. PMID 7270737.

[13] Marques C, Nardi AE, Mendlowicz M, Figueira I, Andrade Y, Camisão C, et al. (1994). "A tranilcipromina no tratamento do transtorno obsessivoðcompulsivo: relato de seis casos" [The tranylcypromine in the treatment of obsessive-compulsive disorder: Report of six cases]. Jornal Brasileiro de Psiquiatria (in Brazilian Portuguese). pp. 400–403.

[14] Joffe RT, Swinson RP (1990). "Tranylcypromine in primary obsessive-compulsive disorder". Journal of Anxiety Disorders. 4 (4): 365–367. doi:10.1016/0887-6185(90)90033-6.

[15] Nardi AE, Lopes FL, Valença AM, Freire RC, Nascimento I, Veras AB, et al. (February 2010). "Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with panic disorder comorbid with social anxiety disorder". Psychiatry Research. 175 (3): 260–265. doi:10.1016/j.psychres.2008.06.025. PMID 20036427. S2CID 45566164.

[16] Saeed SA, Bruce TJ (May 1998). "Panic disorder: effective treatment options". American Family Physician. 57 (10): 2405–2412. PMID 9614411.

[pmid28579071-17] ^ ^a ^b ^c ^d ^e ^f ^g Ricken R, Ulrich S, Schlattmann P, Adli M (August 2017). "Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression". Eur Neuropsychopharmacol. 27 (8): 714–731. doi:10.1016/j.euroneuro.2017.04.003. PMID 28579071. S2CID 30987747.

[pmid31834088-18] Ulrich S, Ricken R, Buspavanich P, Schlattmann P, Adli M (2020). "Efficacy and Adverse Effects of Tranylcypromine and Tricyclic Antidepressants in the Treatment of Depression: A Systematic Review and Comprehensive Meta-analysis". J Clin Psychopharmacol. 40 (1): 63–74. doi:10.1097/JCP.0000000000001153. PMID 31834088. S2CID 209343653.

[pmid21192146-19] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Gillman PK (February 2011). "Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors". Journal of Clinical Psychopharmacology. 31 (1): 66–74. doi:10.1097/JCP.0b013e31820469ea. PMID 21192146. S2CID 10525989.

[pmid28655495-20] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ Ulrich S, Ricken R, Adli M (August 2017). "Tranylcypromine in mind (Part I): Review of pharmacology". European Neuropsychopharmacology. 27 (8): 697–713. doi:10.1016/j.euroneuro.2017.05.007. PMID 28655495. S2CID 4913721.

[Kim_2014-21] Kim MJ, Kim KS (2014). "Tyramine production among lactic acid bacteria and other species isolated from kimchi". LWT - Food Science and Technology. 56 (2): 406–413. doi:10.1016/j.lwt.2013.11.001.

[22] Gillman PK (2016). "Monoamine oxidase inhibitors: a review concerning dietary tyramine and drug interactions" (PDF). PsychoTropical Commentaries. 1: 1–90.

[23] van Haelst IM, van Klei WA, Doodeman HJ, Kalkman CJ, Egberts TC (August 2012). "Antidepressive treatment with monoamine oxidase inhibitors and the occurrence of intraoperative hemodynamic events: a retrospective observational cohort study". The Journal of Clinical Psychiatry. 73 (8): 1103–9. doi:10.4088/JCP.11m07607. PMID 22938842.

[24] Smith MS, Muir H, Hall R (February 1996). "Perioperative management of drug therapy, clinical considerations". Drugs. 51 (2): 238–59. doi:10.2165/00003495-199651020-00005. PMID 8808166. S2CID 46972638.

[25] Blom-Peters L, Lamy M (1993). "Monoamine oxidase inhibitors and anesthesia: an updated literature review". Acta Anaesthesiologica Belgica. 44 (2): 57–60. PMID 8237297.

[26] 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 Psychiatry. 111 (473): 357–364. doi:10.1192/bjp.111.473.357. S2CID 145562899.

[pmid16793513-27] 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 & Biology. 13 (6): 563–7. doi:10.1016/j.chembiol.2006.05.004. PMID 16793513.

[28] Mast N, Charvet C, Pikuleva IA, Stout CD (October 2010). "Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain". The Journal of Biological Chemistry. 285 (41): 31783–95. doi:10.1074/jbc.M110.143313. PMC 2951250. PMID 20667828.

[pmid22022344-29] Gaweska H, Fitzpatrick PF (October 2011). "Structures and Mechanism of the Monoamine Oxidase Family". Biomolecular Concepts. 2 (5): 365–377. doi:10.1515/BMC.2011.030. PMC 3197729. PMID 22022344.

[30] Sherry RL, Rauw G, McKenna KF, Paetsch PR, Coutts RT, Baker GB (December 2000). "Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine". Journal of Affective Disorders. 61 (1–2): 23–9. doi:10.1016/s0165-0327(99)00188-3. PMID 11099737.

[31] A US patent 4016204 A, Rajadhyaksha VJ, "Method of synthesis of trans-2-phenylcyclopropylamine", published 1977-04-05, assigned to Nelson Research & Development Company

[32] Burger A, Yost WL (1948). "Arylcycloalkylamines. I. 2-Phenylcyclopropylamine". Journal of the American Chemical Society. 70 (6): 2198–2201. doi:10.1021/ja01186a062.

[33] López-Muñoz F, Alamo C (2009). "Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today". Current Pharmaceutical Design. 15 (14): 1563–86. doi:10.2174/138161209788168001. PMID 19442174.

[isbn0-19-536874-6-34] Shorter E (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-536874-1.

[35] Atchley DW (September 1964). "Reevaluation of Tranylcypromine Sulfate(Parnate Sulfate)". JAMA. 189 (10): 763–4. doi:10.1001/jama.1964.03070100057011. PMID 14174054.

[pmid26881714-36] Zheng YC, Yu B, Jiang GZ, Feng XJ, He PX, Chu XY, et al. (2016). "Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment". Current Topics in Medicinal Chemistry. 16 (19): 2179–88. doi:10.2174/1568026616666160216154042. PMID 26881714.

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@@ Line 1: / Line 1: @@
+{{Short description|Irreversible non-selective MAO inhibitor Antidepressant drug}}
+{{cs1 config|name-list-style=vanc|display-authors=6}}
 {{Infobox drug
 | Verifiedfields = changed
 | Watchedfields = changed
 | verifiedrevid = 402690453
-| drug_name =
-| type =
-| IUPAC_name = (±)-''trans''-2-phenylcyclopropan-1-amine<br />or<br />''rel''-(1''R'',2''S'')-2-phenylcyclopropan-1-amine
 | image = Tranylcypromine.svg
 | width = 175
 | alt =
 | caption = (1''S'',2''R'')-(−)-tranylcypromine (top),<br />(1''R'',2''S'')-(+)-tranylcypromine (bottom)
-| chirality = [[Racemic mixture]]
-<!--Clinical data-->| tradename = Parnate, many generics<ref name=generics/>
+<!--Clinical data-->
+| tradename = Parnate, many generics<ref name=generics/>
-| synonyms = tran</u>s''-2-phen<u>ylcy</u>clo<u>pro</u>pyla<u>mine
 | Drugs.com = {{drugs.com|monograph|tranylcypromine-sulfate}}
 | MedlinePlus = a682088
@@ Line 22: / Line 20: @@
 | pregnancy_category =
 | legal_AU = S4
+| legal_BR = C1
+| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |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=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
 | legal_CA = Rx-only
 | legal_UK = POM
 | legal_US = Rx-only
 | legal_status = Rx-only
-| routes_of_administration = [[Mouth|Oral]]
+| routes_of_administration = [[Oral administration|Oral]]
+<!--Pharmacokinetic data-->
-<!--Pharmacokinetic data-->| bioavailability = 50%<ref name="Foye's">{{cite book | last = Williams | first = David A. | name-list-style = vanc | chapter = Antidepressants | chapter-url = https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA590 |editor1=Foye, William O. |editor2=Lemke, Thomas L. |editor3=Williams, David A. | 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>
+| 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=2019-12-06}}</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 }}</ref>
 | elimination_half-life = 2.5 hours<ref name="Foye's"/>
 | excretion = [[Urine]], [[Feces]]<ref name="Foye's"/>
-<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}}
+<!--Identifiers-->
+| CAS_number_Ref = {{cascite|correct|??}}
 | CAS_number = 155-09-9
 | ATC_prefix = N06
@@ Line 50: / Line 52: @@
 | KEGG_Ref = {{keggcite|changed|kegg}}
 | KEGG = D08625
+| synonyms = ''trans''-2-Phen<u>ylcy</u>clo<u>pro</u>pyla<u>mine</u>
-<!--Chemical data-->| C = 9
+<!--Chemical data-->
+| IUPAC_name = (±)-''trans''-2-phenylcyclopropan-1-amine<br />or<br />''rel''-(1''R'',2''S'')-2-phenylcyclopropan-1-amine
-| H = 11
-| N = 1
+| C=9 | H=11 | N=1
-| smiles = c1cccc(c1)[C@@H]2C[C@H]2N
+| 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 trade name '''Parnate''' among others)<ref name=generics>Drugs.com [https://www.drugs.com/international/tranylcypromine.html International brands for Tranylcypromine]. Page accessed April 17, 2016</ref> is a [[monoamine oxidase inhibitor]] (MAOI); 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 | last = Baldessarini | first = Ross J. |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.
+'''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 a [[propylamine]] formed from the [[cyclization]] of [[amphetamine]]'s [[side chain]];<!--see the DrugBank or PubChem compound summary for tranylcypromine--> therefore, it is classified as a [[substituted amphetamine]].
+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]].
 ==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>UK Electronic medicines compendium. [https://www.medicines.org.uk/emc/medicine/25577 Tranylcypromine] Llast updated October 28, 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"/>
+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 web | 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}}</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]]
@@ Line 81: / Line 89: @@
 {{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>
-[[Tyramine]] is a common component in many foods, and is normally rapidly metabolized by [[Monoamine oxidase A|MAO-A]]. Individuals not taking MAOIs may consume at least 2 grams of tyramine in a meal and not experience an increase in blood pressure, whereas those taking MAOIs such as tranylcypromine may experience a sharp increase in blood pressure following consumption of as little as 10&nbsp;mg of tyramine, which can lead to hypertensive crisis.<ref name="PMID28655495"/><ref name="pmid21192146"/>
+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.
-Foods containing tyramine include [[aged cheese]]s, [[cured meat]]s, [[tofu]] and certain [[red wine]]s. Some, such as [[yeast extract]]s, contain enough tyramine to be potentially fatal in a single serving. [[Spoiled food]] is also likely to contain dangerous levels of tyramine.<ref name=EMC/>
 ==Adverse effects==
+'''<big>Incidence of adverse effects</big>'''<ref name="pmid28579071" />
-'''<big>Incidence of adverse effects</big>'''<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 = European Neuropsychopharmacology | volume = 27 | issue = 8 | pages = 714–731 | date = August 2017 | pmid = 28579071 | doi = 10.1016/j.euroneuro.2017.04.003 | s2cid = 30987747 | doi-access = free }}</ref>
 '''Very common (>10% incidence) adverse effects include:'''
@@ Line 92: / Line 100: @@
 '''Common (1-10% incidence) adverse effects include:'''
-* [[Tachycardia]] (5-10%)
+* [[Tachycardia]] (5–10%)
 * [[Hypomania]] (7%)
 * [[Paresthesia]] (5%)
@@ Line 124: / Line 132: @@
 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"/>
+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 120–600&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}}</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"/>
+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/>
@@ Line 132: / Line 140: @@
 Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.<ref name=EMC/>
-== Interactions ==
+==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"/>
@@ Line 144: / Line 151: @@
 ==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]], 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.
+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"/>
+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 = free }}</ref> The clinical relevance of this effect is unknown.
+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 }}</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|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"/>
+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"/>
+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"/>
@@ Line 166: / Line 174: @@
 ===Synthesis===
-[[File:Tranylcypromine-synth.png|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|invent1=Vithal Jagannath Rajadhyaksha|assign1=Nelson Research & Development Company|}}</ref>]]
+[[File:Tranylcypromine-synth.png|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}}</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>
+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}}</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 | last = Shorter | first = Edward | name-list-style = vanc | 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"/>
+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 | display-authors = 6 | 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 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 ==
+==See also==
-* [[Phenelzine]]
-* [[Amphetamine]]
-* [[Cibenzoline]] (also based on cyclopropane)
-* [[Ticagrelor]] (contains 3',4'-difluoro-tranylcypromine [[structural motif]])
 * [[Tranylcypromine/trifluoperazine]]
-== References ==
+==References==
 {{Reflist}}
@@ Line 195: / Line 199: @@
 [[Category:Cyclopropanes]]
+[[Category:CYP2D6 inhibitors]]
 [[Category:Monoamine oxidase inhibitors]]
 [[Category:Norepinephrine-dopamine releasing agents]]
 [[Category:Substituted amphetamines]]
+[[Category:Substances discovered in the 1940s]]

v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine Phenpromethamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-AL 3C-BZ 3C-E 3C-MAL 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA ZDCM-04 Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L-Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D-Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D-DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L-DOPA (Levodopa) L-DOPS (Droxidopa) L-Phenylalanine L-Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101 Venlafaxine