isocarboxazid

{{Short description|Irreversible non-selective Monoamine Oxidase Inhibitor Antidepressant}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 416403788

| IUPAC_name = N′-benzyl-5-methylisoxazole-3-carbohydrazide

| image = Isocarboxazid structure.svg

| image_class = skin-invert-image

| width = 250px

| image2 = Isocarboxazid ball-and-stick model from xtal 1996.png

| width2 = 250px

| tradename = Marplan, Enerzer

| Drugs.com = {{drugs.com|CDI|isocarboxazid}}

| MedlinePlus = a605036

| pregnancy_US = C

| legal_AU = S4

| legal_BR = C1

| legal_BR_comment = {{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}}

| legal_CA =

| legal_DE =

| legal_NZ =

| legal_UK =

| legal_US =

| legal_EU =

| legal_UN =

| legal_status = Rx-only

| routes_of_administration = By mouth

| bioavailability = Low, peak at 1–2 h{{cite book | vauthors = Owens DC, Johnstone EC, Lawrie SM | chapter = Clinical psychopharmacology. | title = Companion to psychiatric studies. | date = January 2010 | pages = 227–294 | doi = 10.1016/B978-0-7020-3137-3.00011-5 | isbn = 9780702031373 }}

| metabolism = Liver (Carboxylesterase{{cite journal | vauthors = Moroi K, Kuga T | title = Inhibitory effect of leptophos on carboxylesterase (isocarboxazid amidase) in rat liver | journal = Toxicology Letters | volume = 11 | issue = 1–2 | pages = 81–85 | date = April 1982 | pmid = 6178187 | doi = 10.1016/0378-4274(82)90110-2 }})

| elimination_half-life = 1.5–4 h

| excretion = Urine

| metabolites = Hippuric acid{{cite web|url=https://go.drugbank.com/reactions/2399|website=go.drugbank.com|access-date=27 October 2021|title=Reaction: Isocarboxazid to 1 product}}

| IUPHAR_ligand = 7204

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 59-63-2

| ATC_prefix = N06

| ATC_suffix = AF01

| PubChem = 3759

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

| DrugBank = DB01247

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3628

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 34237V843T

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D02580

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201168

| C = 12

| H = 13

| N = 3

| O = 2

| smiles = O=C(NNCc1ccccc1)c2noc(c2)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C12H13N3O2/c1-9-7-11(15-17-9)12(16)14-13-8-10-5-3-2-4-6-10/h2-7,13H,8H2,1H3,(H,14,16)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = XKFPYPQQHFEXRZ-UHFFFAOYSA-N

}}

Isocarboxazid, sold under the brand name Marplan among others, is a non-selective irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class used as an antidepressant.{{cite journal | vauthors = Fagervall I, Ross SB | title = Inhibition of monoamine oxidase in monoaminergic neurones in the rat brain by irreversible inhibitors | journal = Biochemical Pharmacology | volume = 35 | issue = 8 | pages = 1381–1387 | date = April 1986 | pmid = 2870717 | doi = 10.1016/0006-2952(86)90285-6 }} Along with phenelzine and tranylcypromine, it is one of only three classical MAOIs still available for clinical use in the treatment of psychiatric disorders in the United States,{{cite book| vauthors = Rosenberg D |title=Pocket Guide For The Textbook Of Pharmacotherapy For Child And Adolescent Psychiatric Disorders|url=https://books.google.com/books?id=fep_AAAAQBAJ&pg=PA176|date=21 August 2013|publisher=Routledge|isbn=978-1-134-86002-9|pages=176–}}{{cite book| vauthors = Labbate LA, Fava M, Rosenbaum JF, Arana GW |title=Handbook of Psychiatric Drug Therapy|url=https://books.google.com/books?id=xrZfcE8MydIC&pg=PA99|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-5307-1|pages=99–}} though it is not as commonly employed in comparison to the others.

Isocarboxazid is primarily used to treat mood and anxiety disorders. It has also been investigated in the treatment of schizophrenia,{{cite journal | vauthors = Darling HF | title = Isocarboxazid (marplan) in ambulatory psychiatric patients | journal = The American Journal of Psychiatry | volume = 116 | issue = 4 | pages = 355–356 | date = October 1959 | pmid = 13814129 | doi = 10.1176/ajp.116.4.355 }} Parkinson's disease, and other dementia-related disorders.{{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 | publisher = Experimental Neurology }}

Isocarboxazid, as well as other MAOIs, increase the levels of the monoamine neurotransmitters serotonin, dopamine, norepinephrine, epinephrine, melatonin, and phenethylamine in the brain.{{cite journal | vauthors = Volz HP, Gleiter CH | title = Monoamine oxidase inhibitors. A perspective on their use in the elderly | journal = Drugs & Aging | volume = 13 | issue = 5 | pages = 341–55 | date = November 1998 | pmid = 9829163 | doi = 10.2165/00002512-199813050-00002 | s2cid = 71158339 }}

Classical MAOIs, including isocarboxazid, are used only rarely due to prominent food and drug interactions and have been largely superseded by newer antidepressants such as the selective serotonin reuptake inhibitors (SSRIs). The cause of the interactions is because MAOIs inhibit the metabolism of dietary amines (e.g., tyramine) and the monoamine neurotransmitters. In combination with other drugs that increase the levels of the monoamine neurotransmitters such as the SSRIs, or with certain foods high in dietary amines such as aged cheeses, MAOIs can produce dangerous elevations of monoamine neurotransmitters resulting in potentially life-threatening syndromes such as hypertensive crisis and serotonin syndrome.