{{Short description|Opioid analgesic}} {{dist|Dextromethorphan|Dextrorphan|3-Methoxymorphinan}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 462091038 | IUPAC_name = (1''R'',9''R'',10''R'')-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.0<sup>1</sup>,<sup>10</sup>.0<sup>2</sup>,<sup>7</sup>]heptadeca-2(7),3,5-triene | image = Levomethorphan.svg | image_class = skin-invert-image | image2 = Levometorfan.png | image_class2 = bg-transparent

<!--Clinical data-->| tradename = | MedlinePlus = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | legal_AU = S9 | legal_BR = A1 | 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 = Schedule I | legal_US = Schedule II | dependency_liability = High | addiction_liability = High | legal_UK = Class A | legal_DE = Anlage I

<!--Pharmacokinetic data-->| elimination_half-life = 3-6 hours

<!--Identifiers-->| CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 125-70-2 | ATC_prefix = None | PubChem = 5362449 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4642423 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 7ZZ22K9QE6 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 146176 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1908323 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D12696

<!--Chemical data-->| C = 18 | H = 25 | N = 1 | O = 1 | smiles = COc1ccc2C[C@@H]3[C@@H]4CCCC[C@]4(CCN3C)c2c1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18+/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = MKXZASYAUGDDCJ-CGTJXYLNSA-N }}

'''Levomethorphan (LVM)''' (INN, BAN) is an opioid analgesic of the morphinan family that has never been marketed.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |url= https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA656 |date=14 November 2014 |publisher=Springe |isbn=978-1-4757-2085-3 |pages=656– }}</ref> It is the <small>L</small>-stereoisomer of racemethorphan (methorphan).<ref name="Elks2014" /> The effects of the two isomers of racemethorphan are quite different, with dextromethorphan (DXM) being an antitussive at low doses and a disassociative at much higher doses.<ref name="Hornback2005">{{cite book| vauthors = Hornback JM |title=Organic Chemistry|url=https://books.google.com/books?id=FETzRWMGt3YC&pg=PA243|date=31 January 2005|publisher=Cengage Learning|isbn=0-534-38951-1|pages=243–}}</ref> Levomethorphan is about five times stronger than morphine.<ref>{{cite book | vauthors = Wainer IW | chapter = Toxicology Through a Looking Glass: Stereochemical Questions and Some Answers | chapter-url = https://books.google.com/books?id=3qjUKyL7BokC&pg=PA21 | veditors = Wong SH, Sunshine I | publisher = CRC Press | date = 1996 | title = Handbook of Analytical Therapeutic Drug Monitoring and Toxicology | isbn = 9780849326486 }}</ref>

Levomethorphan is a prodrug to levorphanol, analogously to DXM acting as a prodrug to dextrorphan or codeine behaving as a prodrug to morphine.<ref name="GudinFudin2015">{{cite journal | vauthors = Gudin J, Fudin J, Nalamachu S | title = Levorphanol use: past, present and future | journal = Postgraduate Medicine | volume = 128 | issue = 1 | pages = 46–53 | date = January 2016 | pmid = 26635068 | doi = 10.1080/00325481.2016.1128308 | s2cid = 3912175 }}</ref> As such, levomethorphan has similar effects to levorphanol but is less potent as it must be demethylated to the active form by liver enzymes before being able to produce its effects.<ref name="GudinFudin2015" /> As a prodrug of levorphanol, levomethorphan functions as a potent agonist of all three of the opioid receptors, μ, κ (κ<sub>1</sub> and κ<sub>3</sub> but notably not κ<sub>2</sub>), and δ, as an NMDA receptor antagonist, and as a serotonin-norepinephrine reuptake inhibitor.<ref name="GudinFudin2015" /> Via activation of the κ-opioid receptor, levomethorphan can produce dysphoria and psychotomimetic effects such as dissociation and hallucinations.<ref name="BrueraPortenoy2009">{{cite book| vauthors = Bruera ED, Portenoy RK |title=Cancer Pain: Assessment and Management|url=https://books.google.com/books?id=2TJ-_oECXM4C&pg=PA215|date=12 October 2009|publisher=Cambridge University Press|isbn=978-0-521-87927-9|pages=215–}}</ref>

Levomethorphan is listed under the Single Convention on Narcotic Drugs 1961 and is regulated like morphine in most countries. In the United States it is a Schedule II Narcotic controlled substance with a DEA ACSCN of 9210 and a 2014 annual aggregate manufacturing quota of 195&nbsp;grams, up from 6&nbsp;grams the year before. The salts in use are the tartrate (free base conversion ratio 0.644) and hydrobromide (0.958).<ref>{{Cite web | url = http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html | title = Conversion Factors for Controlled Substances | work = DEA Diversion Control Division | publisher = U.S. Department of Justice, Drug Enforcement Administration (DEA) | access-date = 2014-06-18 | archive-date = 2016-03-02 | archive-url = https://web.archive.org/web/20160302162948/http://deadiversion.usdoj.gov/quotas/conv_factor/index.html | url-status = dead }}</ref> As of February 2026{{when|date=February 2026}}, no levomethorphan pharmaceuticals are marketed in the United States.{{cn|date=February 2026}}

== See also == * Butorphanol * Cyclorphan * Levallorphan * Levorphanol * Nalbuphine * Oxilorphan * Proxorphan * Racemorphan * Xorphanol

== References == {{Reflist}}

{{Analgesics}} {{Hallucinogens}} {{Navboxes | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 = {{GABA receptor modulators}} {{Glycine receptor modulators}} {{Ionotropic glutamate receptor modulators}} {{Monoamine reuptake inhibitors}} {{Opioid receptor modulators}} }}{{Ionotropic glutamate receptor modulators}}

Category:Delta-opioid receptor agonists Category:Enantiopure drugs Category:GABA receptor antagonists Category:Glycine receptor antagonists Category:Hallucinogenic kappa-opioid receptor agonists Category:NMDA receptor antagonists Category:Morphinans Category:Mu-opioid receptor agonists Category:Nociceptin receptor agonists Category:Phenol ethers Category:Prodrugs Category:Semisynthetic opioids Category:Serotonin–norepinephrine reuptake inhibitors