Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Phenelzine: Difference between pages

{{Short description|Antidepressant}}

{{Use dmy dates|date=August 2023}}

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{{Infobox drug

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| verifiedrevid = 464200075

| image = Phenelzine2DACS.svg

| alt =

| image2 = Phenelzine3Dan2.gif

| alt2 = <!-- Clinical data -->

| pronounce =

| tradename = Nardil, others

| Drugs.com = {{drugs.com|monograph|phenelzine-sulfate}}

| DailyMedID = Phenelzine

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Phenelzine (Nardil) Use During Pregnancy | website=Drugs.com | date=3 March 2020 | url=https://www.drugs.com/pregnancy/phenelzine.html | access-date=11 July 2020}}</ref>

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]]

| class = [[Monoamine oxidase inhibitor]]; [[Antidepressant]]

| ATCvet =

| ATC_prefix = N06

| ATC_suffix = AF03

| ATC_supplemental = <!-- Legal status -->

| legal_AU = S4

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| 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 = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

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| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

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| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

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| legal_US = Rx-only

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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

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<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}

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| IUPHAR_ligand = 7266

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

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| synonyms = 2-Phenylethylhydrazine; β-Phenylethylhydrazine; Phenethylhydrazine; Phenylethylhydrazine; Phenylethylamine hydrazide; Phenethylamine hydrazide; β-Hydrazinoethylbenzene; Fenelzine; 1-(2-Phenylethyl)hydrazine

<!-- Chemical data -->| IUPAC_name = 2-phenylethylhydrazine

| C = 8

| H = 12

| N = 2

| SMILES = N(N)CCc1ccccc1

| StdInChI_comment =

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| boiling_point = 74

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'''Phenelzine''', sold under the brand name '''Nardil''' among others, is a [[binding selectivity|non-selective]] and [[irreversible inhibition|irreversible]] [[monoamine oxidase inhibitor]] (MAOI) of the [[hydrazine (antidepressant)|hydrazine]] family which is primarily used as an [[antidepressant]] and [[anxiolytic]] to treat [[depression (mood)|depression]] and [[anxiety]].<ref>{{cite web |title=Phenelzine | work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine |url=https://medlineplus.gov/druginfo/meds/a682089.html |access-date=2023-10-27 |language=en}}</ref> Along with [[tranylcypromine]] and [[isocarboxazid]], phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.<ref name = "Sidhu_2023">{{cite book | vauthors = Sidhu G, Marwaha R | chapter = Phenelzine |date=2023 |chapter-url= http://www.ncbi.nlm.nih.gov/books/NBK554508/ | title = StatPearls |access-date=2023-11-23 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119395 }}</ref>

Synthesis of phenelzine was first described by [[Emil Votoček]] and Otakar Leminger in 1932.<ref>{{cite book | vauthors = Budavari S, O'Neil, Smith A, Heckelman PE, Kinneary JF | chapter = Phenelzine | id = 7181 | title = [[The Merck Index]] | edition = 12th | location = Whitehouse Station | publisher = Merck & Co | year = 1996 }}</ref><ref>{{cite journal | vauthors = Votoček E, Leminger O | author-link1 = Emil Votoček | title = Sur la β-phenoéthylhydrazine. | trans-title = On the [preparation and properties of] β-phenoethylhydrazine | language = French | journal = Collection of Czechoslovak Chemical Communications | date = 1932 | volume = 4 | pages = 271–281 | doi = 10.1135/cccc19320271 }}</ref>

==Medical uses==

Phenelzine is primarily used in the [[therapy|treatment]] of [[major depressive disorder]] (MDD). Patients with depressive symptomology characterized as "[[Atypical depression|atypical]]," "nonendogenous," and/or "neurotic" respond particularly well to phenelzine.<ref>{{cite web | author = Parke-Davis Division of Pfizer Inc. | date = 2007 | title = Nardil(R) (Phenelzine sulfate tablets, USP), labeling information | access-date = 14 December 2009 | publisher = U.S. Food and Drug Administration's |url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf |url-status=live |archive-url= https://web.archive.org/web/20091127225136/http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf |archive-date=27 November 2009 }}</ref> The medication is also useful in patients who do not respond favorably to first and second-line treatments for depression, or are "[[Treatment-resistant depression|treatment-resistant]]."<ref>{{cite journal | vauthors = Fiedorowicz JG, Swartz KL | title = The role of monoamine oxidase inhibitors in current psychiatric practice | journal = Journal of Psychiatric Practice | volume = 10 | issue = 4 | pages = 239–248 | date = July 2004 | pmid = 15552546 | pmc = 2075358 | doi = 10.1097/00131746-200407000-00005 }}</ref> In addition to being a recognized treatment for major depressive disorder, phenelzine is effective in treating [[dysthymia]],<ref>{{cite journal | vauthors = Vallejo J, Gasto C, Catalan R, Salamero M | title = Double-blind study of imipramine versus phenelzine in Melancholias and Dysthymic Disorders | journal = The British Journal of Psychiatry | volume = 151 | issue = 5 | pages = 639–642 | date = November 1987 | pmid = 3446308 | doi = 10.1192/bjp.151.5.639 | s2cid = 145651628 }}</ref> [[bipolar depression]] (BD),<ref>{{cite journal | vauthors = Quitkin FM, McGrath P, Liebowitz MR, Stewart J, Howard A | title = Monoamine oxidase inhibitors in bipolar endogenous depressives | journal = Journal of Clinical Psychopharmacology | volume = 1 | issue = 2 | pages = 70–74 | date = March 1981 | pmid = 7028797 | doi = 10.1097/00004714-198103000-00005 | s2cid = 32909169 }}</ref> [[panic disorder]] (PD),<ref>{{cite journal | vauthors = Buigues J, Vallejo J | title = Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks | journal = The Journal of Clinical Psychiatry | volume = 48 | issue = 2 | pages = 55–59 | date = February 1987 | pmid = 3542985 }}</ref> [[social anxiety disorder]],<ref>{{cite journal | vauthors = Blanco C, Schneier FR, Schmidt A, Blanco-Jerez CR, Marshall RD, Sánchez-Lacay A, Liebowitz MR | title = Pharmacological treatment of social anxiety disorder: a meta-analysis | journal = Depression and Anxiety | volume = 18 | issue = 1 | pages = 29–40 | year = 2003 | pmid = 12900950 | doi = 10.1002/da.10096 | s2cid = 12296484 }}</ref> [[bulimia|bulimia nervosa]],<ref>{{cite journal | vauthors = Walsh BT, Gladis M, Roose SP, Stewart JW, Stetner F, Glassman AH | title = Phenelzine vs placebo in 50 patients with bulimia | journal = Archives of General Psychiatry | volume = 45 | issue = 5 | pages = 471–475 | date = May 1988 | pmid = 3282482 | doi = 10.1001/archpsyc.1988.01800290091011 }}</ref> [[post-traumatic stress disorder]] (PTSD),<ref>{{cite journal | vauthors = Frank JB, Kosten TR, Giller EL, Dan E | title = A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder | journal = The American Journal of Psychiatry | volume = 145 | issue = 10 | pages = 1289–1291 | date = October 1988 | pmid = 3048121 | doi = 10.1176/ajp.145.10.1289 }}</ref> and [[obsessive-compulsive disorder|obsessive–compulsive disorder]] (OCD).<ref>{{cite journal | vauthors = Vallejo J, Olivares J, Marcos T, Bulbena A, Menchón JM | title = Clomipramine versus phenelzine in obsessive-compulsive disorder. A controlled clinical trial | journal = The British Journal of Psychiatry | volume = 161 | issue = 5 | pages = 665–670 | date = November 1992 | pmid = 1422616 | doi = 10.1192/bjp.161.5.665 | s2cid = 36232956 }}</ref><ref>{{cite journal | vauthors = Grant JE, Baldwin DS, Chamberlain SR | title = Time to Reconsider Monoamine Oxidase Inhibitors for Obsessive Compulsive Disorder?: A Case Series Using Phenelzine | journal = Journal of Clinical Psychopharmacology | volume = 41 | issue = 4 | pages = 461–464 | date = July 2021 | pmid = 34108430 | doi = 10.1097/JCP.0000000000001418 | s2cid = 235395484 | url = https://eprints.soton.ac.uk/450147/1/OCD_phenelzine_3_27_21.docx }}</ref>

==Side effects==

Common side effects of phenelzine may include [[dizziness]], [[blurry vision]], [[dry mouth]], [[headache]], [[lethargy]], [[sedation]], [[somnolence]], [[insomnia]], [[Anorexia (symptom)|anorexia]], [[weight gain]] or [[weight loss|loss]], [[small fiber peripheral neuropathy]], [[nausea]] and [[vomiting]], [[diarrhea]], [[constipation]], [[urinary retention]], [[mydriasis]], [[muscle tremor]]s, [[hyperthermia]], [[sweating]], [[hypertension]] or [[hypotension]], [[orthostatic hypotension]], [[paresthesia]], [[hepatitis]], and [[sexual dysfunction]] (consisting of loss of [[libido]] and [[anorgasmia]]). Rare side effects usually only seen in susceptible individuals may include [[hypomania]] or [[mania]], [[psychosis]] and [[acute liver failure]], the last of which is usually only seen in people with pre-existing [[liver damage]], [[old age]], [[long-term effects of alcohol consumption]], or [[viral infection]].<ref>{{cite journal | vauthors = Gómez-Gil E, Salmerón JM, Mas A | title = Phenelzine-induced fulminant hepatic failure | journal = Annals of Internal Medicine | volume = 124 | issue = 7 | pages = 692–693 | date = April 1996 | pmid = 8607601 | doi = 10.7326/0003-4819-124-7-199604010-00014 | s2cid = 43020372 }}</ref>

==Interactions==

{{See also|Monoamine oxidase inhibitor#Dangers}}

{{See also|Foods containing tyramine}}

The MAOIs have certain dietary restrictions and drug interactions. A [[hypertensive crisis]] may result from the overconsumption of [[tyramine]]-containing foods, although it is a rare occurrence.<ref>{{cite journal |vauthors=Gillman PK |title=The risk of harm from acute tyramine-induced hypertension: how significant? |journal=PsychoTropical Commentaries |volume=5 |pages=1–10 |date=January 2019 |doi=10.13140/RG.2.2.11909.40165 |url=https://psychotropical.com/risk_of_harm_from_acute_tyr_hypertension/ |access-date=8 January 2022 |archive-date=8 January 2022 |archive-url=https://web.archive.org/web/20220108155939/https://psychotropical.com/risk_of_harm_from_acute_tyr_hypertension/ |url-status=dead }}{{self-published inline|date=January 2022}}</ref><ref>{{cite journal | vauthors = Grady MM, Stahl SM | title = Practical guide for prescribing MAOIs: debunking myths and removing barriers | journal = CNS Spectrums | volume = 17 | issue = 1 | pages = 2–10 | date = March 2012 | pmid = 22790112 | doi = 10.1017/S109285291200003X | s2cid = 206312008 }}</ref> [[Serotonin syndrome]] may result from an interaction with certain drugs which increase serotonin activity such as [[selective serotonin reuptake inhibitors]], [[serotonin releasing agent]]s, and [[serotonin]] [[agonist]]s.<ref>{{cite journal | vauthors = Scotton WJ, Hill LJ, Williams AC, Barnes NM | title = Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions | journal = International Journal of Tryptophan Research | volume = 12 | pages = 1178646919873925 | year = 2019 | pmid = 31523132 | pmc = 6734608 | doi = 10.1177/1178646919873925 }}</ref><ref>{{cite journal | vauthors = Volpi-Abadie J, Kaye AM, Kaye AD | title = Serotonin syndrome | journal = Ochsner Journal | volume = 13 | issue = 4 | pages = 533–540 | year = 2013 | pmid = 24358002 | pmc = 3865832 }}</ref>

Phenelzine has also been linked to [[vitamin B6|vitamin B₆]] [[Vitamin B6#Deficiency|deficiency]].<ref>{{cite journal | vauthors = Malcolm DE, Yu PH, Bowen RC, O'Donovan C, Hawkes J, Hussein M | title = Phenelzine reduces plasma vitamin B6 | journal = Journal of Psychiatry & Neuroscience | volume = 19 | issue = 5 | pages = 332–334 | date = November 1994 | pmid = 7803366 | pmc = 1188621 }}</ref> Transaminases such as [[GABA-transaminase]] have been shown to be dependent upon vitamin B₆<ref name="Storici_2004">{{PDB|1OHW}}; {{cite journal | vauthors = Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T | title = Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin | journal = The Journal of Biological Chemistry | volume = 279 | issue = 1 | pages = 363–373 | date = January 2004 | pmid = 14534310 | doi = 10.1074/jbc.M305884200 | doi-access = free }}</ref> and may be involved in a potentially related process, since the phenelzine metabolite phenylethylidenehydrazine (PEH) is a GABA-transaminase inhibitor. Both phenelzine and vitamin B₆ are rendered inactive upon these reactions occurring. The pyridoxine form of B₆ is recommended for supplementation, since this form has been shown to reduce [[Hydrazine (antidepressant)|hydrazine]] toxicity from phenelzine and, in contrast, the [[Pyridoxal phosphate|pyridoxal]] form has been shown to increase the toxicity of hydrazines.<ref>{{cite journal | vauthors = Dubnick B, Leeson GA, Scott CC | title = Effect of forms of vitamin B6 on acute toxicity of hydrazines | journal = Toxicology and Applied Pharmacology | volume = 2 | issue = 4 | pages = 403–409 | date = July 1960 | pmid = 13818307 | doi = 10.1016/0041-008X(60)90007-7 }}</ref>

==Pharmacology==

===Pharmacodynamics===

Phenelzine is a non-selective and [[Irreversible inhibition|irreversible inhibitor]] of the [[enzyme]] [[monoamine oxidase]] (MAO). It inhibits both of the respective [[isoform]]s of MAO, [[MAO-A]] and [[MAO-B]], and does so almost equally, with a slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the [[monoamine]] [[neurotransmitter]]s [[serotonin]], [[melatonin]], [[norepinephrine]], [[epinephrine]], and [[dopamine]], as well as the [[trace amine]] [[neuromodulator]]s such as [[phenethylamine]], [[tyramine]], [[octopamine]], and [[tryptamine]]. This leads to an increase in the [[extracellular]] [[concentration]]s of these [[neurochemical]]s and, therefore, an alteration in [[neurochemistry]] and [[neurotransmission]]. This action is thought to be the primary mediator in phenelzine's [[therapeutic benefit]]s.<ref>{{cite journal | vauthors = Baker GB, Coutts RT, McKenna KF, Sherry-McKenna RL | title = Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review | journal = Journal of Psychiatry & Neuroscience | volume = 17 | issue = 5 | pages = 206–214 | date = November 1992 | pmid = 1362653 | pmc = 1188458 }}</ref>

Phenelzine and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are [[alanine transaminase]] (ALA-T),<ref>{{cite journal | vauthors = Tanay VA, Parent MB, Wong JT, Paslawski T, Martin IL, Baker GB | title = Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain | journal = Cellular and Molecular Neurobiology | volume = 21 | issue = 4 | pages = 325–339 | date = August 2001 | pmid = 11775064 | doi = 10.1023/A:1012697904299 | s2cid = 20655821 }}</ref> and [[4-aminobutyrate—pyruvate transaminase|γ-aminobutyric acid transaminase]] (GABA-T),<ref>{{cite book | vauthors = McKenna KF, McManus DJ, Baker GB, Coutts RT | chapter = Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: Effects on GABAergic function | title = Amine Oxidases: Function and Dysfunction | series = Journal of Neural Transmission. Supplementum | volume = 41 | pages = 115–122 | year = 1994 | pmid = 7931216 | doi = 10.1007/978-3-7091-9324-2_15 | isbn = 978-3-211-82521-1 | veditors = Tipton KF, Youdim MB, Barwell CJ, Callingham BA, Lyles GA }}</ref> the latter of which is not caused by phenelzine itself, but by a phenelzine metabolite [[phenylethylidenehydrazine]] (PEH). By inhibiting ALA-T and GABA-T, phenelzine causes an increase in the [[alanine]] and [[GABA]] levels in the brain and body.<ref>{{cite thesis | vauthors = Paslawski TM | degree = Ph.D. | publisher = University of Alberta | url = https://library-archives.canada.ca/eng/services/services-libraries/theses/Pages/item.aspx?idNumber=46576166 |title=The Antipanic Drug Phenelzine and Its Effects on GABA and Related Amino Acids |year=1998 | isbn = 978-0-612-29091-4 | oclc = 46576166 }}</ref> GABA is the major [[inhibitory]] neurotransmitter in the [[mammalian]] [[central nervous system]], and is very important for the normal suppression of anxiety, stress, and depression. Phenelzine's action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have been considered superior to those of other antidepressants. As for ALA-T inhibition, though the consequences of disabling this enzyme are currently not well understood, there is some evidence to suggest that it is this action of the hydrazines (including phenelzine) which may be responsible for the occasional incidence of [[hepatitis]] and [[liver failure]].<ref>{{cite journal | vauthors = Gómez-Gil E, Salmerón JM, Mas A | title = Phenelzine-induced fulminant hepatic failure | journal = Annals of Internal Medicine | volume = 124 | issue = 7 | pages = 692–693 | date = April 1996 | doi = 10.7326/0003-4819-124-7-199604010-00014 | pmid = 8607601 }}</ref>

Phenelzine has also been shown to metabolize to phenethylamine (PEA).<ref name="pmid4004908">{{cite journal | vauthors = Dyck LE, Durden DA, Boulton AA | title = Formation of beta-phenylethylamine from the antidepressant, beta-phenylethylhydrazine | journal = Biochemical Pharmacology | volume = 34 | issue = 11 | pages = 1925–1929 | date = June 1985 | pmid = 4004908 | doi = 10.1016/0006-2952(85)90310-7 }}</ref> PEA acts as a [[releasing agent]] of norepinephrine and dopamine, which occurs in a similar manner to [[amphetamine]] by being taken up into vesicles, displacing and causing the release of those monoamines, and reversing monoamine flux through their respective transporters (though with markedly shorter pharmacokinetics).<ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref>

Like many other antidepressants, phenelzine usually requires several weeks of treatment to achieve full therapeutic effects. The reason for this delay is not fully understood. Still, it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, the possibility of necessary [[downregulation|desensitization]] of [[autoreceptor]]s which generally inhibit the release of neurotransmitters like serotonin and dopamine, and also the upregulation of enzymes such as [[serotonin N-acetyltransferase]]. Typically, a therapeutic response to MAOIs is associated with an inhibition of at least 80-85% of monoamine oxidase activity.<ref>{{cite journal | vauthors = Raft D, Davidson J, Wasik J, Mattox A | title = Relationship between response to phenelzine and MAO inhibition in a clinical trial of phenelzine, amitriptyline and placebo | journal = Neuropsychobiology | volume = 7 | issue = 3 | pages = 122–126 | year = 1981 | pmid = 7231652 | doi = 10.1159/000117841 }}</ref>

===Pharmacokinetics===

[[Image:NardilTablets.jpg|thumb|right|Phenelzine 15 mg tablets.]]Phenelzine is administered orally in the form of phenelzine sulfate<ref name = "Sidhu_2023" /> and is rapidly absorbed from the [[gastrointestinal tract]].<ref>{{cite web |title=Phenelzine |url=https://go.drugbank.com/drugs/DB00780 |access-date=2023-11-23 |website=go.drugbank.com |language=en}}</ref> The time to peak plasma concentration is 43 minutes, and the half-life is 11.6 hours.<ref>{{cite web |title=Phenelzine: Package Insert |url=https://www.drugs.com/pro/phenelzine.html |access-date=2023-11-23 |website=Drugs.com |language=en}}</ref> Unlike most other drugs, phenelzine irreversibly disables MAO. As a result, it does not necessarily need to be present in the blood at all times for its effects to be sustained. Because of this, upon phenelzine treatment being ceased, its effects typically do not wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks.<ref name = "Sidhu_2023" />

Phenelzine is [[metabolized]] primarily in the liver, and its [[metabolite]]s are excreted in the urine. Oxidation is the primary routine of metabolism, and the major metabolites are phenylacetic acid and parahydroxyphenylacetic acid, recovered as about 73% of the excreted dose of phenelzine in the urine over 96 hours after single doses. Acetylation to N²-acetylphenelzine is a minor pathway.<ref>{{Cite web |title=NARDIL- phenelzine sulfate tablet, film coated |url=https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=513a41d0-37d4-4355-8a6d-a2c643bce6fa&type=pdf |url-status=live |archive-url=https://web.archive.org/web/20240520175554/https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=513a41d0-37d4-4355-8a6d-a2c643bce6fa |archive-date=2024-05-20 |archive-format=PDF |access-date=2024-05-20 |website=[[DailyMed]] |format=PDF}}</ref><ref>{{cite journal | vauthors = Kallem RR, Jillela B, Ravula AR, Samala R, Andy A, Ramesh M, Rao JS | title = Highly sensitive LC-MS/MS-ESI method for determination of phenelzine in human plasma and its application to a human pharmacokinetic study | journal = Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences | volume = 1022 | pages = 126–132 | date = June 2016 | pmid = 27085800 | doi = 10.1016/j.jchromb.2016.04.006 }}</ref> Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through the formation of a heme adduct.<ref>{{cite journal | vauthors = Polasek TM, Elliot DJ, Somogyi AA, Gillam EM, Lewis BC, Miners JO | title = An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid | journal = British Journal of Clinical Pharmacology | volume = 61 | issue = 5 | pages = 570–584 | date = May 2006 | pmid = 16669850 | pmc = 1885050 | doi = 10.1111/j.1365-2125.2006.02627.x }}</ref> Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine.<ref>{{cite journal | vauthors = Matveychuk D, MacKenzie EM, Kumpula D, Song MS, Holt A, Kar S, Todd KG, Wood PL, Baker GB | title = Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine | journal = Cellular and Molecular Neurobiology | volume = 42 | issue = 1 | pages = 225–242 | date = January 2022 | pmid = 33839994 | pmc = 8732914 | doi = 10.1007/s10571-021-01078-3 }}</ref>

==Chemistry==

Phenelzine, also known as 2-phenylethylhydrazine or phenylethylamine hydrazide, is a [[substituted phenethylamine|phenethylamine]] and [[hydrazine]] [[chemical derivative|derivative]].<ref name="ShulginManningDaley2011" /><ref name="IsomerDesign2024">{{cite web | title=PiHKAL·info | website=Isomer Design | date=4 August 2024 | url=https://isomerdesign.com/pihkal/explore/10642 | access-date=12 August 2024}}</ref> It is the [[hydrazide]] of [[β-phenethylamine]] and can also be referred to as ''N''-aminophenethylamine.<ref name="ShulginManningDaley2011">{{cite book | vauthors = Shulgin A, Manning T, Daley DF | title=[[The Shulgin Index|The Shulgin Index: Psychedelic Phenethylamines and Related Compounds]] | publisher=Transform Press | volume = 1 | year=2011 | isbn=978-0-9630096-3-0 | quote = [...] phenelzine (N-amino-phenethylamine, an anxiolytic) [...]}}</ref><ref name="IsomerDesign2024" />

Close [[structural analog|analogue]]s of phenelzine include the [[substituted amphetamine|amphetamine]] and hydrazine derivatives [[pheniprazine]] (α-methylphenelzine; the corresponding [[amphetamine]] analogue) and [[metfendrazine]] (α,''N''-dimethylphenelzine; the corresponding [[methamphetamine]] analogue), among others.<ref name="SecciBolascoChimenti2011">{{cite journal | vauthors = Secci D, Bolasco A, Chimenti P, Carradori S | title = The state of the art of pyrazole derivatives as monoamine oxidase inhibitors and antidepressant/anticonvulsant agents | journal = Curr Med Chem | volume = 18 | issue = 33 | pages = 5114–5144 | date = 2011 | pmid = 22050759 | doi = 10.2174/092986711797636090 | url = }}</ref><ref name="YáñezPadínArranz-Tagarro2012">{{cite journal | vauthors = Yáñez M, Padín JF, Arranz-Tagarro JA, Camiña M, Laguna R | title = History and therapeutic use of MAO-A inhibitors: a historical perspective of MAO-A inhibitors as antidepressant drug | journal = Curr Top Med Chem | volume = 12 | issue = 20 | pages = 2275–2282 | date = 2012 | pmid = 23231399 | doi = 10.2174/156802612805220011 | url = }}</ref>

==Research==

Phenelzine showed promise in a phase II clinical trial from March 2020 in treating [[prostate cancer]].<ref name="Stone_2020">{{cite journal | vauthors = Stone L | title = MAOA inhibitor phenelzine efficacious in recurrent prostate cancer | journal = Nature Reviews. Urology | volume = 17 | issue = 4 | pages = 192 | date = April 2020 | pmid = 32203303 | doi = 10.1038/s41585-020-0307-y | s2cid = 212681980 | doi-access = free }}

*{{lay source |template = cite news |vauthors = McDonald R|url= https://www.curetoday.com/view/antidepressant-appears-safe-effective-in-men-with-biochemical-recurrent-prostate-cancer|title = Antidepressant Appears Safe, Effective in Men with Biochemical Recurrent Prostate Cancer|date = 25 March 2020 |website = Curetoday.com}}</ref> Phenelzine has also been shown to have [[Neuroprotection|neuroprotective effects]] in animal models.<ref name="Baker_2019">{{cite journal | vauthors = Baker G, Matveychuk D, MacKenzie EM, Holt A, Wang Y, Kar S | title = Attenuation of the effects of oxidative stress by the MAO-inhibiting antidepressant and carbonyl scavenger phenelzine | journal = Chemico-Biological Interactions | volume = 304 | issue = | pages = 139–147 | date = May 2019 | pmid = 30857888 | doi = 10.1016/j.cbi.2019.03.003 | s2cid = 75140657 | url = | doi-access = free | bibcode = 2019CBI...304..139B }}</ref><ref>{{cite journal | vauthors = Matveychuk D, MacKenzie EM, Kumpula D, Song MS, Holt A, Kar S, Todd KG, Wood PL, Baker GB | title = Overview of the Neuroprotective Effects of the MAO-Inhibiting Antidepressant Phenelzine | journal = Cellular and Molecular Neurobiology | volume = 42 | issue = 1 | pages = 225–242 | date = January 2022 | pmid = 33839994 | doi = 10.1007/s10571-021-01078-3 | pmc = 8732914 | s2cid = 233211407 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Cebak JE, Singh IN, Hill RL, Wang JA, Hall ED | title = Phenelzine Protects Brain Mitochondrial Function In Vitro and In Vivo following Traumatic Brain Injury by Scavenging the Reactive Carbonyls 4-Hydroxynonenal and Acrolein Leading to Cortical Histological Neuroprotection | journal = Journal of Neurotrauma | volume = 34 | issue = 7 | pages = 1302–1317 | date = April 2017 | pmid = 27750484 | pmc = 5385448 | doi = 10.1089/neu.2016.4624 }}</ref>

==References==

{{Reflist}}

{{Antidepressants}}

{{Anxiolytics}}

{{Monoamine metabolism modulators}}

{{GABA metabolism and transport modulators}}

{{Hydrazines}}

{{Phenethylamines}}

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[[Category:GABA transaminase inhibitors]]

[[Category:Hepatotoxins]]

[[Category:Hydrazines]]

[[Category:Monoamine oxidase inhibitors]]

[[Category:Phenethylamines]]

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