Tranylcypromine
Clinical data | |
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Trade names | Parnate, many generics[1] |
Other names | trans-2-phenylcyclopropylamine |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682088 |
Pregnancy category |
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Routes of administration | Oral |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 50%[4] |
Metabolism | Liver[5][6] |
Elimination half-life | 2.5 hours[4] |
Excretion | Urine, Feces[4] |
Identifiers | |
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JSmol) | |
Chirality | Racemic mixture |
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Tranylcypromine, sold under the brand name Parnate among others,
Tranylcypromine is a
.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.[8] It is also used in depression that is not responsive to reuptake inhibitor antidepressants, such as the SSRIs, TCAs, or bupropion.[9] In addition to being a recognized treatment for major depressive disorder, tranylcypromine has been demonstrated to be effective in treating
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.[15][16]
Contraindications
Contraindications include:[8][9][17]
- 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. [18][17][19]
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.[20][19] 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[15]
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.[15]
Tranylcypromine is not associated with
It is generally recommended that MAOIs be discontinued prior to
Tranylcypromine abuse has been reported at doses ranging from 120 to 600 mg per day.[8][24][15] 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.[15]
Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation.[8]
Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.[8]
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:[17]
- Dexmedetomidine
- nicotine
- TSNAs (found in cured tobacco products, including cigarettes)
- Valproate
Pharmacology
Pharmacodynamics
Tranylcypromine acts as a nonselective and irreversible inhibitor of monoamine oxidase. The clinical relevance of increased trace amine availability is unclear.
It may also act as a
Tranylcypromine has also been shown to inhibit the
Tranylcypromine has been found to inhibit
Pharmacokinetics
Tranylcypromine reaches its maximum concentration (tmax) within 1–2 hours.[18] After a 20 mg dose, plasma concentrations reach at most 50-200 ng/mL.[18] While its half-life is only about 2 hours, its pharmacodynamic effects last several days to weeks due to irreversible inhibition of MAO.[18]
Metabolites of tranylcypromine include 4-hydroxytranylcypromine, N-acetyltranylcypromine, and N-acetyl-4-hydroxytranylcypromine, which are less potent MAO inhibitors than tranylcypromine itself.[18] Amphetamine was once thought to be a metabolite of tranylcypromine, but has not been shown to be.[18][28][17]
Tranylcypromine inhibits CYP2A6 at therapeutic concentrations.[17]
Chemistry
Synthesis
History
Tranylcypromine was originally developed as an
The drug was introduced by
Research
Tranylcypromine is known to inhibit LSD1, an enzyme that selectively demethylates two lysines found on histone H3.[25][18][34] Genes promoted downstream of LSD1 are involved in cancer cell growth and metastasis, and several tumor cells express high levels of LSD1.[34] Tranylcypromine analogues with more potent and selective LSD1 inhibitory activity are being researched in the potential treatment of cancers.[34][35]
Tranylcypromine may have neuroprotective properties applicable to the treatment of Parkinson's disease, similar to the MAO-B inhibitors selegiline and rasagiline.[36][9] 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.[9]
See also
References
- ^ a b Drugs.com International brands for Tranylcypromine. Page accessed April 17, 2016
- 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.
- ^ ISBN 978-0-7817-6879-5.
- ^ "Tranylcypromine". www.drugbank.ca. Retrieved 2019-12-06.
- S2CID 21380176.
- ^ ISBN 978-0-07-142280-2.
- ^ a b c d e UK Electronic medicines compendium. Tranylcypromine Llast updated October 28, 2015
- ^ PMID 22110357.
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- ^ Marques C, Nardi A, Mendlowicz M, Figueira I, Versiani M (1994-01-01). "The tranylcypromine in the treatment of obsessive-compulsive disorder: Report of six cases". ResearchGate. pp. 400–403.
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- ^ Gillman PK (2016). "Monoamine oxidase inhibitors: a review concerning dietary tyramine and drug interactions" (PDF). PsychoTropical Commentaries. 1: 1–90.
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- ^ A US patent 4016204 A, Vithal Jagannath Rajadhyaksha, "Method of synthesis of trans-2-phenylcyclopropylamine", published 1977-04-05, assigned to Nelson Research & Development Company
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