Wikipedia

Oxilofrine

Not to be confused withOxyfedrine.

Oxilofrine,sold under the brand namesCarnigenandSuprifenamong others, is asympathomimeticmedicationwhich has been used as anantihypotensive agentandcough suppressant.[4][5][6]It is takenby mouth.[1]

Oxilofrine
Clinical data
Trade namesCarnigen, Cophylac, Suprifen, others
Other namesOxilophrine; Hydroxyephedrine; (±)-Hydroxyephedrine; 4-Hydroxyephedrine;p-Hydroxyephedrine; Oxyephedrine; Methylsynephrine; 4-HMP; 4,β-Dihydroxy-N-methyl-α-methylphenethylamine; 4,β-Dihydroxy-N-methylamphetamine
Routes of
administration		Oral[1]
ATC code
  • None
Legal status
Legal status
Identifiers
  • (1S*,2R*)-(±)-4-(1-Hydroxy-2-methylamino-propyl)phenol
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.006.067Edit this at Wikidata
Chemical and physical data
FormulaC10H15NO2
Molar mass181.235g·mol−1
  • InChI=1S/C10H15NO2/c1-7(11-2)10(13)8-3-5-9(12)6-4-8/h3-7,10-13H,1-2H3checkY
  • Key:OXFGTKPPFSCSMA-UHFFFAOYSA-NcheckY
(verify)

Oxilofrine acts as anorepinephrine releasing agentand hence is an indirectly acting sympathomimetic.[7][6][8]It is asubstituted amphetamineand is closely related toephedrine(with oxilofrine also being known as 4-hydroxyephedrine).[4][8]

Oxilofrine was first developed in the 1930s.[9]It is mostly no longer marketed today.[10]

Pharmacology

edit

Oxilofrine is described as anephedrine-like indirectly actingsympathomimeticandantihypotensive agent.[4][7][6]It acts as anorepinephrine releasing agentand indirectly activates theα-andβ-adrenergic receptors.[6][8]The drug haspositive inotropiceffects (increasesmyocardial contractility).[6]

Chemistry

edit

Oxilofrine, also known as 4,β-dihydroxy-N-methyl-α-methylphenethylamine or as 4,β-dihydroxy-N-methylamphetamine, is asubstituted phenethylamineandamphetaminederivative.[4][10]It is theracemic4-hydroxylatedanalogueofephedrine((1R,2S)-β-hydroxy-N-methylamphetamine).[4]It is also related topholedrine(4-hydroxy-N-methylamphetamine).[4]

The predictedlog Pof oxilofrine ranges from -0.13 to 0.6.[11][1][12]It is morehydrophilicthan ephedrine, which has an experimental log P of 1.13 and a predicted log P of 0.9 to 1.32.[13][14][15]

History

edit

Oxilofrine was originally developed in the 1930s as acardiac stimulant.Trade names included Suprifen (Bayer) and, combined with anadenosine-containing standardized organ extract, Carnigen (Hoechst AG).[9]

In combination withnormethadone,it was marketed as acough suppressantunder the trade name Ticarda. As of 2021, this formulation was still manufactured in Canada byValeantand sold as Cophylac.[16]

Several other sympathomimetics andvasodilatorswere developed as chemical derivatives of oxilofrine, such as theβ2-adrenergic receptoragonistsbuphenineandisoxsuprine.[17][18]

Society and culture

edit

Names

edit

Oxilofrineis thegeneric nameof the drug and itsINNTooltip International Nonproprietary Name.[4][7][10]It is also known by synonyms includingmethylsynephrine,oxyphedrine,andhydroxyephedrine.[4][10]Brand names of oxilofrine includeCarnigen,Cophylac(withnormethadone),Suprifen,andTicarda(also with normethadone), among others.[4][10][9]

Availability

edit

Oxilofrine has been marketed inAustria,Canada,andGermany.[4][10]

Use in exercise and sports

edit

Oxilofrine is currently aWorld Anti-Doping Agency(WADA) prohibited substance when used in competition.[19]It has been found as anadulterantin some dietary supplements.[9][20]Even after receiving warning letters from the FDA,[21]some sports and weight loss supplement companies continue to use oxilofrine as an undeclared ingredient in their products despite it being prohibited.[22]

List of doping cases

edit

Severaldopingcases involving oxilofrine have been publicized, including:

  • In 2009, Brazilian/American cyclistFlávia Oliveirawas suspended for 2 years after taking a supplement known as "HyperDrive 3.0+" which contained methylsynephrine, a chemical equivalent of oxilofrine, among other substances.[23]Her sentence was eventually reduced to 18 months after an appeal as there was enough evidence that she had unknowingly consumed said substance as the old label did not list methylsynephrine.[24]
  • On 18 September 2010, Vietnamese weightlifterHoàng Anh Tuấn,silver medalist in2008 Summer Olympicswas handed a four year ban, later reduced to two years, for testing positive with the substance. It was found out that the substance came from unlabeled drinks he consumed during his training in China.[25]
  • On July 14, 2013, Jamaican runnersAsafa PowellandSherone Simpsontested positive for oxilofrine prior to the2013 World Athletics Championships.[26]Powell, however, maintained that he did not take any banned supplements knowingly or willfully.[27]Powell voluntarily withdrew as a result of the test. On 10 April 2014, both athletes received an 18-month suspension from competing, which was set to expire in December that year.[28]However, after appealing to theCourt of Arbitration for Sport(CAS), both athletes' suspensions were lifted on 14 July 2014.[29]
  • On July 16, 2015,Red Soxpitching prospectMichael Kopechwas suspended without pay for 50 games after testing positive for oxilofrine, which is a banned substance under the Minor League Drug Prevention and Treatment Program. Kopech denied knowingly taking the substance.[30]
  • In October 2018, theWBOstripped boxerBilly Joe Saundersof its middleweight world title after he tested positive for oxilofrine, as a result of a drug test administered by the Voluntary Anti-Doping Association (VADA). In his defense, Saunders held that while the substance was proscribed by VADA it was not banned "out of competition" byUK Anti-Doping,or theBritish Boxing Board of Control,but this appeal was rejected.[31]

Other drugs

edit

Oxilofrine is a knownmetaboliteofpara-methoxymethamphetamine(PMMA).[6]

References

edit
  1. ^abc"Oxilofrine: Uses, Interactions, Mechanism of Action".DrugBank Online.31 December 1957.Retrieved1 September2024.
  2. ^"Methylsynephrine in Dietary Supplements".FDA.February 22, 2023.RetrievedJune 9,2023.
  3. ^Anvisa(2023-03-31)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 2023-04-04).Archivedfrom the original on 2023-08-03.Retrieved2023-08-16.
  4. ^abcdefghijSchweizerischer Apotheker-Verein (2000).Index Nominum 2000: International Drug Directory.Medpharm Scientific Publishers. p. 772.ISBN978-3-88763-075-1.Retrieved2024-09-01.
  5. ^Fourcroy JL (2008).Pharmacology, doping and sports: a scientific guide for athletes, coaches, physicians, scientists and administrators.Taylor & Francis.ISBN978-0-415-42845-3.
  6. ^abcdefDocherty JR (June 2008)."Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)".Br J Pharmacol.154(3): 606–622.doi:10.1038/bjp.2008.124.PMC2439527.PMID18500382.
  7. ^abcMorton IK, Hall JM (2012).Concise Dictionary of Pharmacological Agents: Properties and Synonyms.Springer Netherlands. p. 211.ISBN978-94-011-4439-1.Retrieved2024-09-01.
  8. ^abcDerendorf H (1995).Drug Actions: Basic Principles and Theraputic Aspects.CRC-Press. p. 227.ISBN978-0-8493-7774-7.Retrieved1 September2024.
  9. ^abcdCohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA (January 2017)."Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA".Drug Testing and Analysis.9(1): 135–142.doi:10.1002/dta.1976.PMID27062112.
  10. ^abcdef"Oxilofrine".drugs.com.2013-07-17. Archived fromthe originalon 2016-04-13.Retrieved2024-09-01.
  11. ^"Suprifen".PubChem.Retrieved1 September2024.
  12. ^"oxilofrine".ChemSpider.1 September 2024.Retrieved1 September2024.
  13. ^"Ephedrine".PubChem.Retrieved30 August2024.
  14. ^"Ephedrine: Uses, Interactions, Mechanism of Action".DrugBank Online.29 April 2016.Retrieved14 July2024.
  15. ^"L-(−)-Ephedrine".ChemSpider.30 August 2024.Retrieved30 August2024.
  16. ^"Prescribing Information Including Patient Medication Information – Cophylac® Drops"(PDF).Valeant Canada. 2010-01-17.Retrieved2022-01-06.
  17. ^Külz F, Schneider M (1950). "Über neue gefäßerweiternde Sympathomimetika" [On new vasodilating sympathomimetics].Klin Wochenschr(in German).28(31–32): 535–537.doi:10.1007/BF01481535.PMID14775050.
  18. ^Freedman L (1955). "Arlidin: a new vasodilative sympathomimetic drug".Angiology.6(1): 52–58.doi:10.1177/000331975500600106.PMID14350296.S2CID46317963.
  19. ^"Substances Prohibited In-Competition".WADA.Archived fromthe originalon 2013-07-02.Retrieved2013-07-15.
  20. ^Zovko Končić M (April 2018)."Getting More Than You Paid For: Unauthorized" Natural "Substances in Herbal Food Supplements on EU Market".Planta Medica.84(6–07): 394–406.doi:10.1055/s-0044-100042.PMID29341031.
  21. ^"Products & Ingredients - Methylsynephrine in Dietary Supplements".Center for Food Safety and Applied Nutrition.U.S. Food and Drug Administration. 22 October 2020.
  22. ^Cohen PA, Wen A, Gerona R (December 2018)."Prohibited Stimulants in Dietary Supplements After Enforcement Action by the US Food and Drug Administration".JAMA Internal Medicine.178(12): 1721–1723.doi:10.1001/jamainternmed.2018.4846.PMC6583602.PMID30422217.
  23. ^Pelkey C (2010-04-13)."Oliveira suspended for two years".Velonews.Archivedfrom the original on 2015-10-06.
  24. ^Pelkey C (2011-02-24)."Court of Arbitration for Sport reduces Flavia Oliveira suspension".Velonews.Archivedfrom the original on 2015-12-23.
  25. ^"Dính doping, lực sỹ Hoàng Anh Tuấn bị cấm thi đấu 2 năm".dantri.com.vn.22 January 2011.
  26. ^"Jamaicans Powell, Simpson test positive - SuperSport - Athletics".SuperSport. Reuters.Retrieved2013-07-15.
  27. ^"Jamaican Sprinter Asafa Powell slapped 18-month ban for doping".IANS.news.biharprabha.com.Archivedfrom the original on 14 April 2014.Retrieved10 April2014.
  28. ^"Asafa Powell banned for 18 months for doping".BBC Sport.10 April 2014. Archived fromthe originalon 9 May 2014.
  29. ^"Jamaican sprinters Asafa Powell and Sherone Simpson have doping bans cut".The Guardian.14 July 2014.Retrieved14 July2014.
  30. ^Wild D (16 July 2015)."Red Sox No. 10 prospect Kopech suspended".MiLB.com.Archivedfrom the original on 9 March 2016.Retrieved8 March2016.
  31. ^Worsell E (12 October 2018)."The ins and outs of Billy Joe Saunders, oxilofrine and VADA".Boxing News.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Oxilofrine&oldid=1258042166"