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. 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). Oxilofrine was first developed in the 1930s. It is mostly no longer marketed today.

Pharmacology

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).

Chemistry

Oxilofrine, also known as 4,β-dihydroxy-N-methyl-α-methylphenethylamine or as 4,β-dihydroxy-N-methylamphetamine, is a substituted phenethylamine and amphetamine derivative. It is the racemic 4-hydroxylated analogue of ephedrine ((1R,2S)-β-hydroxy-N-methylamphetamine). It is also related to pholedrine (4-hydroxy-N-methylamphetamine). The predicted log P of oxilofrine ranges from -0.13 to 0.6. It is more hydrophilic than ephedrine, which has an experimental log P of 1.13 and a predicted log P of 0.9 to 1.32.

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). 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. Several other sympathomimetics and vasodilators were developed as chemical derivatives of oxilofrine, such as the β2-adrenergic receptor agonists buphenine and isoxsuprine.

Society and culture

Names

Oxilofrine is the generic name of the drug and its INN. 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.

Availability

Oxilofrine has been marketed in Austria, Canada, and Germany.

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.

List of doping cases

Several doping cases involving oxilofrine have been publicized, including:

Other drugs

Oxilofrine is a known metabolite of para-methoxymethamphetamine (PMMA).