Levomethorphan

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 462091038

| IUPAC_name = (1R,9R,10R)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5-triene

| image = Levomethorphan.svg

| image_class = skin-invert-image

| image2 = Levometorfan.png

| image_class2 = bg-transparent

| tradename =

| MedlinePlus =

| pregnancy_AU =

| pregnancy_US =

| legal_AU = S9

| legal_BR = A1

| 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 = Schedule I

| legal_US = Schedule II

| dependency_liability = High

| addiction_liability = High

| legal_UK = Class A

| legal_DE = Anlage I

| elimination_half-life = 3-6 hours

| 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

| 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.{{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– }} It is the L-stereoisomer of racemethorphan (methorphan). The effects of the two isomers of racemethorphan are quite different, with dextromethorphan (DXM) being an antitussive at low doses and a dissociative hallucinogen at much higher doses.{{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–}} Levomethorphan is about five times stronger than morphine.{{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 }}

Levomethorphan is a prodrug to levorphanol, analogously to DXM acting as a prodrug to dextrorphan or codeine behaving as a prodrug to morphine.{{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 }} 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. As a prodrug of levorphanol, levomethorphan functions as a potent agonist of all three of the opioid receptors, μ, κ (κ₁ and κ₃ but notably not κ₂), and δ, as an NMDA receptor antagonist, and as a serotonin-norepinephrine reuptake inhibitor. Via activation of the κ-opioid receptor, levomethorphan can produce dysphoria and psychotomimetic effects such as dissociation and hallucinations.{{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–}}

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 grams, up from 6 grams the year before. The salts in use are the tartrate (free base conversion ratio 0.644) and hydrobromide (0.958).{{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 }} At the current time{{when|date=January 2024}}, no levomethorphan pharmaceuticals are marketed in the United States.{{cn|date=January 2024}}