β₂ -Adrenoceptor agonist activity of higenamine

Area of Science:

• Pharmacology
• Anti-doping science
• Molecular biology

Background:

• Higenamine is listed on the World Anti-Doping Agency (WADA) Prohibited Substances List as a beta-2 adrenoceptor agonist.
• Its prohibition applies to both in-competition and out-of-competition testing.

Purpose of the Study:

• To review the physiology and pharmacology of adrenoceptors.
• To summarize existing literature on higenamine's mechanism of action.
• To present new in silico and in vitro data on higenamine's activity.

Main Methods:

• Literature review of adrenoceptor physiology and higenamine's action.
• In silico computational analysis to predict receptor interaction.
• In vitro experiments using Chinese hamster ovary (CHO) cells expressing human beta-2 adrenoceptors.

Main Results:

• Existing studies suggest higenamine acts as a beta-2 adrenoceptor agonist.
• In silico models predicted higenamine and a metabolite interact with the beta-2 receptor.
• In vitro assays confirmed higenamine's agonist activity at beta-2 receptors, aligning with in silico predictions.

Conclusions:

• The study confirms and expands upon previous findings regarding higenamine's mechanism of action.
• Data strongly support the classification of higenamine as a beta-2 adrenoceptor agonist.
• These findings validate the inclusion of higenamine on the WADA Prohibited List.