{{Short description|Opioid analgesic}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464200012 | IUPAC_name = (2''R'',6''R'',11''R'')-6,11-Dimethyl-3-(2-phenylethyl)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-ol | image = Phenazocine2DCSD.svg | image_class = skin-invert-image | width = 220px | image2 = Phenazocine 3D BS.png | image_class2 = bg-transparent | width2 = 220px
<!--Clinical data--> | tradename = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | legal_AU = Schedule 9 | 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 | legal_CA = Schedule I | legal_UK = Class A | legal_UK_comment = Withdrawn | legal_US = Schedule II | legal_DE = Anlage I | routes_of_administration = Oral
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | excretion =
<!--Identifiers--> | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 58073-76-0 | ATC_prefix = N02 | ATC_suffix = AD02 | PubChem = 14707 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | KEGG = C11790 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 391631 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = J0ND6N0AQC | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 46399
<!--Chemical data--> | C=22 | H=27 | N=1 | O=1 | smiles = C[C@H]1[C@H]2Cc3ccc(cc3[C@@]1(CCN2CCc4ccccc4)C)O | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C22H27NO/c1-16-21-14-18-8-9-19(24)15-20(18)22(16,2)11-13-23(21)12-10-17-6-4-3-5-7-17/h3-9,15-16,21,24H,10-14H2,1-2H3/t16-,21+,22+/m0/s1 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = ZQHYKVKNPWDQSL-KNXBSLHKSA-N | synonyms = Fenazocina, Phenazocinum, DEA No. 9715 }} '''Phenazocine''' (brand names '''Prinadol''', '''Narphen''') is an opioid analgesic drug, which is related to pentazocine and has a similar profile of effects.<ref>{{cite patent | country = US | number = 2959594 | title = Iso-benzmorphan derivatives }}</ref>
Effects of phenazocine include analgesia and euphoria, also may include dysphoria and hallucinations at high doses, most likely due to action at κ-opioid and σ receptors.<ref name="Harris">{{cite journal |vauthors=Harris LS, Pierson AK | title=Some Narcotic Antagonists in the Benzomorphan Series | journal=Journal of Pharmacology and Experimental Therapeutics |date=February 1964 | pages=141–8 | volume= 143| issue=2 | doi=10.1016/S0022-3565(25)26704-0 | pmid=14163985}}</ref> Phenazocine appears to be a much stronger analgesic with fewer side effects than pentazocine, probably due to a more favorable μ/κ binding ratio. Phenazocine is a much more potent analgesic than pentazocine and other drugs in the benzomorphan series, most probably due to the presence of an ''N''-phenethyl substitution, which is known to boost μ-opioid activity in many classes of opioid analgesics.<ref name="Feinberg">{{cite journal |vauthors=Feinberg AP, Creese I, Snyder SH | title=The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists | journal=Proceedings of the National Academy of Sciences USA |date=November 1976 | pages=4215–9 | volume=73 | issue=11 | pmid=186791 | doi=10.1073/pnas.73.11.4215 | pmc= 431391| bibcode=1976PNAS...73.4215F | doi-access=free }}</ref> Also, it does not cause spasm of the sphincter of Oddi, making it more suitable than morphine for the treatment of biliary or pancreatic pain.<ref name="Hopton">{{cite journal | author=Hopton D. | title=Double-blind clinical trial of the analgesic effects of phenazocine hydrobromide (Narphen) compared with morphine sulphate in patients with acute abdominal pain | journal=Gut |date=January 1971 | pages=51–4 | volume=12 | issue= 1 | pmid=4929685 | doi=10.1136/gut.12.1.51 | pmc=1411461}}</ref>
Regarding the two enantiomers of phenazocine, (''R'')-phenazocine{{clarify|There are multiple stereocenters, so the two enantiomers cannot be distinguished as R and S|date=September 2022}} has twenty times the potency of morphine as an analgesic,<ref>{{cite journal | doi=10.1038/184451a0 | title=Identification of Phenazocine, a Potent New Analgesic | journal=Nature | date=August 1959 | volume=184 | issue=4684 | pages=451 | last1=Clarke | first1=E. G. C. | pmid=13810504 | bibcode=1959Natur.184..451C | s2cid=4190489 | doi-access=free }}</ref> while (''S'')-phenazocine has about four times the potency of morphine.<ref>Textbook of Pharmacology - Page 117</ref>{{full|date=September 2022}}
==History== Phenazocine was invented in the 1950s.<ref name="Clarke">{{cite journal | author= Clarke EG | title=Identification of Phenazocine, a Potent New Analgesic | journal=Nature | date=August 8, 1959 | pages=451 | volume= 184 | issue= Suppl 7 | pmid=13810504 | doi= 10.1038/184451a0| bibcode=1959Natur.184..451C | s2cid=4190489 | doi-access=free }}</ref><ref name="Eckenhoff">{{cite journal | author= Eckenhoff JE | title=Phenazocine, a new benzomorphan narcotic analgesic | journal=Anesthesiology | date=May–June 1959 | pages=355–8 | volume=20 | issue=3 | pmid=13650222 | doi= 10.1097/00000542-195905000-00016| s2cid=30670011 }}</ref> It was one of a number of benzomorphan opioids (including pentazocine, dezocine, and cyclazocine) developed in the search for non-addictive strong analgesics.
Phenazocine was once widely used, and was mainly supplied as 5 mg tablets of the hydrobromide salt for sublingual use (Narphen, Prinadol and other names), but its use was discontinued in the United Kingdom in 2001.<ref name="discontinueUK">{{cite web |date=February 2001 | url = http://www.connectingforhealth.nhs.uk/systemsandservices/data/readcodes/docs/tandc0201.pdf | archive-url = http://webarchive.nationalarchives.gov.uk/20081106082526/http://www.connectingforhealth.nhs.uk/systemsandservices/data/readcodes/docs/tandc0201.pdf | url-status = dead | archive-date = 2008-11-06 | title = Monthly Release Terming and Coding Newsletter | publisher = NHS Information Authority | access-date = 2008-01-11}} </ref>
Phenazocine was briefly used in the United States but fell out of favor;{{Citation needed|date=May 2013}} it remains a Schedule II substance under the Comprehensive Drug Abuse Control & Prevention Act (Controlled Substances Act) of 1970 (CSA) but is not manufactured. The DEA ACSCN for phenazocine is 9715 and its 2013 annual manufacturing quota was 6 grams.<ref>{{cite web | title = Quotas - 2013 | url = http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm | work = Diversion Control Division | publisher = Drug Enforcement Agency, U.S. Department of Justice | access-date = 2014-05-30 | archive-date = 2017-05-14 | archive-url = https://web.archive.org/web/20170514115234/https://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0620.htm | url-status = dead }}</ref>
==See also== * Tapentadol - An opioid analgesic with reduced abuse-liability
==References== {{Reflist|2}}
{{Analgesics}} {{Hallucinogens}} {{Opioidergics}}
Category:Benzomorphans Category:Hallucinogenic kappa-opioid receptor agonists Category:Mu-opioid receptor agonists Category:Hydroxyarenes Category:Synthetic opioids