Isomethadone

{{Short description|Opioid analgesic and cough suppressant drug}}

{{Drugbox

| IUPAC_name = (±)-6-(Dimethylamino)-5-methyl-4,4-diphenyl-3-hexanone

| image = Isomethadone structure.svg

| image_class = skin-invert-image

| width = 201

| CAS_number = 466-40-0

| CAS_supplemental =
5341-49-1 (HCl)
26594-41-2 ((R)-form)
561-10-4 ((S)-form)
7487-81-2 ((S)-form (HCl))

| ATC_prefix = None

| ATC_suffix =

| PubChem = 10072

| ChemSpiderID = 9675

| C=21 | H=27 | N=1 | O=1

| smiles = O=C(CC)C(C1=CC=CC=C1)(C(C)CN(C)C)C2=CC=CC=C2

| synonyms = WIN-1783, BW 47-442

| StdInChI = 1S/C21H27NO/c1-5-20(23)21(17(2)16-22(3)4,18-12-8-6-9-13-18)19-14-10-7-11-15-19/h6-15,17H,5,16H2,1-4H3

| StdInChIKey = IFKPLJWIEQBPGG-UHFFFAOYSA-N

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| pregnancy_category =

| legal_DE = Anlage II

| legal_status =

| 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

|legal_UN = P I

| routes_of_administration =

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

| UNII = 12L95QD6KV

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

| KEGG = D12676

}}

Isomethadone (INN, BAN; trade name Liden; also known as isoamidone) is a synthetic opioid analgesic and antitussive related to methadone that was used formerly as a pharmaceutical drug but is now no longer marketed.{{cite book | vauthors = Macdonald F | title = Dictionary of Pharmacological Agents | url = https://books.google.com/books?id=A0THacd46ZsC&pg=PA1169 | access-date = 16 May 2012 | year = 1997 | publisher = CRC Press | isbn = 978-0-412-46630-4 | page = 1169}}{{cite book | vauthors = Morton IK, Hall JM | title = Concise Dictionary of Pharmacological Agents: Properties and Synonyms | url = https://books.google.com/books?id=mqaOMOtk61IC&pg=PA157 | access-date = 16 May 2012 | year = 1999 | publisher = Springer | isbn = 978-0-7514-0499-9 | page = 157}}{{cite journal |vauthors=Keats AS, Beecher HK | title = Analgesic potency and side action liability in man of heptazone, WIN 1161-2, 6-methyl dihydromorphine, Metopon, levo-isomethadone and pentobarbital sodium, as a further effort to refine methods of evaluation of analgesic drugs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 105 | issue = 2 | pages = 109–29 |date=June 1952 | doi = 10.1016/S0022-3565(25)05014-1 | pmid = 14928215 | url = http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14928215| url-access = subscription }}{{cite journal |vauthors=Winter CA, Flataker L | title = Antitussive action of d-isomethadone and d-methadone in dogs | journal = Proceedings of the Society for Experimental Biology and Medicine | publisher = Society for Experimental Biology and Medicine | location = New York, N.Y. | volume = 81 | issue = 2 | pages = 463–5 |date=November 1952 | pmid = 13027341 | doi = 10.3181/00379727-81-19912| s2cid = 36487588 }} Isomethadone was used as both an analgesic and antitussive. It binds to and activates both the μ- and δ-opioid receptors, with the (S)-isomer being the more potent of the two enantiomers.{{cite journal |vauthors=Portoghese PS, Poupaert JH, Larson DL, etal | title = Synthesis, X-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that mu and delta opioid receptors possess different stereochemical requirements | journal = Journal of Medicinal Chemistry | volume = 25 | issue = 6 | pages = 684–8 |date=June 1982 | pmid = 6284938 | doi = 10.1021/jm00348a015}} Isomethadone is a Schedule II controlled substance in the United States, with an ACSCN of 9226 and a 2014 aggregate manufacturing quota of 5 g. The salts in use are the hydrobromide (HBr, free base conversion ratio 0.793), hydrochloride (HCl, 0.894), and HCl monohydrate (0.850).{{cite web |url = http://www.deadiversion.usdoj.gov/fed_regs/quotas/2014/fr0825.htm |title = Final Adjusted Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2014 |work = Code of Federal Regulations |access-date = 2016-02-28 |archive-date = 2016-03-04 |archive-url = https://web.archive.org/web/20160304053357/http://www.deadiversion.usdoj.gov/fed_regs/quotas/2014/fr0825.htm |url-status = dead }} Isomethadone is also regulated internationally as a Schedule I controlled substance under the United Nations Single Convention on Narcotic Drugs of 1961.{{cite book | vauthors = Nordegren T | title = The A-Z Encyclopedia of Alcohol and Drug Abuse | url = https://books.google.com/books?id=4yaGePenGKgC&pg=PA366 | access-date = 16 May 2012 | date = 1 March 2002 | publisher = Universal-Publishers | isbn = 978-1-58112-404-0 | page = 366}}