Oxilofrine

Overview

Oxilofrine, sold under the brand names Carnigen and Suprifen among others, is a sympathomimetic medication which has been used as an antihypotensive agent and cough suppressant. It is taken by mouth.[1–4] WP

Oxilofrine acts as a norepinephrine releasing agent and hence is an indirectly acting sympathomimetic. It is a substituted amphetamine and is closely related to ephedrine (with oxilofrine also being known as 4-hydroxyephedrine).[1][3][5][6] WP

Oxilofrine was first developed in the 1930s. It is mostly no longer marketed today.[7][8] WP

Drug class

Antihypotensive agent Cough suppressant Norepinephrine releasing agent Alpha-adrenergic receptor agonist WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Use in exercise and sports

Oxilofrine is currently a World Anti-Doping Agency (WADA) prohibited substance when used in competition. It has been found as an adulterant in some dietary supplements. Even after receiving warning letters from the FDA, some sports and weight loss supplement companies continue to use oxilofrine as an undeclared ingredient in their products despite it being prohibited.[7][9–12] WP

List of doping cases

Several doping cases involving oxilofrine have been publicized, including: WP

• In 2009, Brazilian/American cyclist Flávia Oliveira was suspended for 2 years after taking a supplement known as "HyperDrive 3.0+" which contained methylsynephrine, a chemical equivalent of oxilofrine, among other substances. 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.[13][14] WP
• On 18 September 2010, Vietnamese weightlifter Hoàng Anh Tuấn, silver medalist in 2008 Summer Olympics was 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.[15] WP
• On July 14, 2013, Jamaican runners Asafa Powell and Sherone Simpson tested positive for oxilofrine prior to the 2013 World Athletics Championships. Powell, however, maintained that he did not take any banned supplements knowingly or willfully. 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. However, after appealing to the Court of Arbitration for Sport (CAS), both athletes' suspensions were lifted on 14 July 2014.[16–19] WP
• On July 16, 2015, Red Sox pitching prospect Michael Kopech was 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.[20] WP
• In October 2018, the WBO stripped boxer Billy Joe Saunders of 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" by UK Anti-Doping, or the British Boxing Board of Control, but this appeal was rejected.[21] WP

Pharmacology

Pharmacodynamics

Oxilofrine is described as an ephedrine-like indirectly acting sympathomimetic and antihypotensive agent. It acts as a norepinephrine releasing agent and indirectly activates the α- and β-adrenergic receptors. The drug has positive inotropic effects (increases myocardial contractility).[1][3][5][6] WP

As an α-adrenergic receptor agonist, Oxilofrine activates the Alpha-1 adrenergic receptor. Activation of said receptor causes vasoconstriction, which is likely how it treats cough. By that mechanism, secretion of mucus into the airway would be dampened, thus reducing the urge to cough. It's also postulated that Oxilofrine acts as a sigma-1 receptor agonist, since it shares structural similarities to dextromethorphan and methamphetamine, two other sigma-1 receptor agonists.[22] WP

History

History

Oxilofrine was originally developed in the 1930s as a cardiac stimulant. Trade names included Suprifen (Bayer) and, combined with an adenosine-containing standardized organ extract, Carnigen (Hoechst AG).[7] WP

In combination with normethadone, it was marketed as a cough suppressant under the trade name Ticarda. As of 2021, this formulation was still manufactured in Canada by Valeant and sold as Cophylac.[23] WP

Several other sympathomimetics and vasodilators were developed as chemical derivatives of oxilofrine, such as the β₂-adrenergic receptor agonists buphenine and isoxsuprine.[24][25] WP

Legal status

Names

Oxilofrine is the generic name of the drug and its INN (International Nonproprietary Name). It is also known by synonyms including methylsynephrine, oxyphedrine, and hydroxyephedrine. Brand names of oxilofrine include Carnigen, Cophylac (with normethadone), Suprifen, and Ticarda (also with normethadone), among others.[1][5][7][8] WP

Availability

Oxilofrine has been marketed in Austria, Canada, and Germany.[1][8] WP

Chemistry

Formula

C10H15NO2 PC

Molar mass (g/mol)

181.23 PC

IUPAC name (computed by PubChem)

4-[1-hydroxy-2-(methylamino)propyl]phenol PC

SMILES

CC(C(C1=CC=C(C=C1)O)O)NC PC

InChIKey

OXFGTKPPFSCSMA-UHFFFAOYSA-N PC

PubChem CID

9701

IUPAC name

(1S*,2R*)-(±)-4-(1-Hydroxy-2-methylamino-propyl)phenol WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Schweizerischer Apotheker-Verein. Index Nominum 2000: International Drug Directory. 2000
2. Other Fourcroy JL. Pharmacology, doping and sports: a scientific guide for athletes, coaches, physicians, scientists and administrators. 2008
3. Journal / agency Docherty JR. Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Br J Pharmacol. June 2008. doi:10.1038/bjp.2008.124 · PMID 18500382 · PMC2439527
4. Harm reduction site Oxilofrine: Uses, Interactions, Mechanism of Action. 31 December 1957
5. Other Morton IK, Hall JM. Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 2012
6. Other Derendorf H. Drug Actions: Basic Principles and Therapeutic Aspects. 1995
7. Journal / agency Cohen PA, Avula B, Venhuis B, Travis JC, Wang YH, Khan IA. Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA. Drug Testing and Analysis. January 2017. doi:10.1002/dta.1976 · PMID 27062112
8. Other Oxilofrine. 2013-07-17
9. Other Substances Prohibited In-Competition
10. Journal / agency Zovko Končić M. Getting More Than You Paid For: Unauthorized "Natural" Substances in Herbal Food Supplements on EU Market. Planta Medica. April 2018. doi:10.1055/s-0044-100042 · PMID 29341031
11. Journal / agency Products & Ingredients - Methylsynephrine in Dietary Supplements. 22 October 2020
12. Journal / agency Cohen PA, Wen A, Gerona R. Prohibited Stimulants in Dietary Supplements After Enforcement Action by the US Food and Drug Administration. JAMA Internal Medicine. December 2018. doi:10.1001/jamainternmed.2018.4846 · PMID 30422217 · PMC6583602
13. Other Pelkey C. Oliveira suspended for two years. 2010-04-13
14. Other Pelkey C. Court of Arbitration for Sport reduces Flavia Oliveira suspension. 2011-02-24
15. Other Dính doping, lực sỹ Hoàng Anh Tuấn bị cấm thi đấu 2 năm. 22 January 2011
16. Other Jamaicans Powell, Simpson test positive - SuperSport - Athletics
17. Other Jamaican Sprinter Asafa Powell slapped 18-month ban for doping
18. Other Asafa Powell banned for 18 months for doping. 10 April 2014
19. Other Jamaican sprinters Asafa Powell and Sherone Simpson have doping bans cut. 14 July 2014
20. Other Wild D. Red Sox No. 10 prospect Kopech suspended. 16 July 2015
21. Other Worsell E. The ins and outs of Billy Joe Saunders, oxilofrine and VADA. 12 October 2018
22. Journal / agency Oxilofrine
23. Harm reduction site Prescribing Information Including Patient Medication Information – Cophylac® Drops. 2010-01-17
24. Journal / agency Külz F, Schneider M. Über neue gefäßerweiternde Sympathomimetika. Klin Wochenschr. 1950. doi:10.1007/BF01481535 · PMID 14775050
25. Journal / agency Freedman L. Arlidin: a new vasodilative sympathomimetic drug. Angiology. 1955. doi:10.1177/000331975500600106 · PMID 14350296

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.