Tranylcypromine

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Tranylcypromine
Tranylcypromine.svg
(1S,2R)-(−)-tranylcypromine (top),
(1R,2S)-(+)-tranylcypromine (bottom)
Systematic (IUPAC) name
(±)-trans-2-phenylcyclopropan-1-amine
or
rel-(1R,2S)-2-phenylcyclopropan-1-amine
Clinical data
Trade names originally Parnate, many generics[1]
AHFS/Drugs.com Monograph
MedlinePlus a682088
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
Routes of
administration
Oral
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)
  • US: ℞-only
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 50%[2]
Metabolism

Liver (MAOA and MAOB)

(CYP2A6, CYP2C19, CYP2D6)
Biological half-life 2.5 hours[2]
Excretion Urine, Feces[2]
Identifiers
CAS Number 155-09-9 YesY
ATC code N06AF04 (WHO)
PubChem CID 19493
DrugBank DB00752 YesY
ChemSpider 18369 YesY
UNII 3E3V44J4Z9 N
ChEBI CHEBI:9652 N
ChEMBL CHEMBL1179 N
Synonyms Transamine
Chemical data
Formula C9H11N
Molar mass 133.19 g/mol
Chirality Racemic mixture
 NYesY (what is this?)  (verify)

Tranylcypromine (INN, USAN, BAN) (originally "Parnate", generic for decades)[1] is a monoamine oxidase inhibitor (MAOI)—it is a nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO).[2][3] It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively.

Clinical use[edit]

Tranylcypromine is used to treat major depressive disorder, especially when there is an anxiety component, typically as a second line treatment.[4]

Contraindications include:[4]

  • Porphyria
  • Cardiovascular or cerebrovascular disease
  • Pheochromocytoma
  • People taking other MAOis, sympathomimetic amines such as amphetamine, fenfluramine or similar anti-obesity agents, ephedrine, levodopa or dopamine, pethidine and closely related narcotic analgesics, nefopam, dextromethorphan, or buspirone

Dietary restrictions[edit]

Like other MAOIs, foods high in endogenous monoamine precursors or exogenous monoamine compounds may cause adverse reactions. The most common example, hypertensive crisis, is caused by the ingestion of tyramine, which is found in foods such as aged cheeses, cured meats, tofu and certain red wines. Some, such as yeast extracts, contain enough tyramine to be potentially fatal in a single serving. Spoiled food is also likely to contain dangerous levels of tyramine.[4]

Adverse effects[edit]

The most common side effect of tranylcypromine is insomnia; other side effects include orthostatic or postural hypotension, dizziness, drowsiness, fatigue, dry mouth, blurred vision, headache, diarrhea, nausea and vomiting, sleep disturbances, rash and rarely hepatocellular damage, jaundice, hallucinations and blood dyscrasias. Overstimulation including anxiety and agitation, developing rarely into hypomanias; severe hypertensive reactions may occur.[4]

At least one case of the abuse of tranylcypromine has been noted.[4][5]

Cases of suicidal ideation and suicidal behaviours have been reported during tranylcypromine therapy or early after treatment discontinuation.[4]

Symptoms of tranylcypromine overdose are generally more intense manifestations of its usual effects.[4]

Pharmacology[edit]

Tranylcypromine 10-mg tablets

Tranylcypromine acts as a nonselective and irreversible inhibitor of monoamine oxidase.[2] Regarding the isoforms of monoamine oxidase, it shows slight preference for the MAOB isoenzyme over MAOA. In addition, tranylcypromine functions as a norepinephrine and dopamine releasing agent with approximately 1/10 the potency of amphetamine.[3]

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.[6]

History[edit]

Tranylcypromine was originally developed as an analog of amphetamine.[2] Although it was first synthesized in 1948,[7] 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.[8]

The drug was introduced by Smith, Kline and French in the United Kingdom in 1960, and approved in the United States in 1961.[9] 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.[10]

See also[edit]

References[edit]

  1. ^ a b Drugs.com International brands for Tranylcypromine. Page accessed April 17, 2016
  2. ^ a b c d e f Williams, David A. (2007). "Antidepressants". In Foye, William O.; Lemke, Thomas L.; Williams, David A. Foye's Principles of Medicinal Chemistry. Hagerstwon, USA: Lippincott Williams & Wilkins. pp. 590–1. ISBN 0-7817-6879-9. 
  3. ^ a b Baldessarini, Ross J. (2005). "17. Drug therapy of depression and anxiety disorders". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. ISBN 0-07-142280-3. 
  4. ^ a b c d e f g UK Electronic medicines compendium. Tranylcypromine Llast updated October 28, 2015
  5. ^ 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. 
  6. ^ 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. 
  7. ^ Burger, A; Yost, WL. "Arylcycloalkylamines. I. 2-Phenylcyclopropylamine". Journal of the American Chemical Society. 70 (6): 2198–2201. doi:10.1021/ja01186a062. 
  8. ^ 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. 
  9. ^ Shorter, Edward (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-536874-6. 
  10. ^ ATCHLEY, DW (September 1964). "Reevaluation of Tranylcypromine Sulfate(Parnate Sulfate)". JAMA. 189: 763–4. doi:10.1001/jama.1964.03070100057011. PMID 14174054. 
  1. REDIRECT Template:Prostanoid signaling modulators
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