Absorption, Biokinetics, and Metabolism of the Dopamine D2 Receptor Agonist Hordenine (N, N-Dimethyltyramine) after Beer Consumption in Humans

J Agric Food Chem. 2020 Feb 19;68(7):1998-2006. doi: 10.1021/acs.jafc.9b06029. Epub 2020 Feb 5.


Hordenine, a natural constituent of germinated barley, is a biased agonist of the dopamine D2 receptor. This pilot study investigated the biokinetics of hordenine and its metabolites in four volunteers consuming beer equal to 0.075 mg hordenine/kg body weight. A new ultrahigh-performance liquid chromatography method coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method determined maximum plasma concentrations of 12.0-17.3 nM free hordenine after 0-60 min. Hordenine phase-II metabolism was first dominated by sulfation, but later by glucuronidation. The elimination half-lives in plasma were 52.7-66.4 min for free hordenine and about 60/80 min longer for hordenine sulfate and hordenine glucuronide. Urinary excretion peaked 2-3.5 h after consumption and accumulated to 3.78 μmol within 24 h, corresponding to 9.9% of the ingested dose. The observed hordenine levels in plasma seem too low to provoke direct interaction with the dopamine D2 receptor related to food reward, but synergistic or additive effects with alcohol or N-methyltyramine may occur.

Keywords: beer; biokinetics; dopamine D2 receptor; hordenine; human metabolism.

MeSH terms

  • Adult
  • Beer / analysis*
  • Chromatography, High Pressure Liquid
  • Dopamine Agonists / blood
  • Dopamine Agonists / pharmacokinetics*
  • Dopamine Agonists / urine
  • Female
  • Humans
  • Male
  • Middle Aged
  • Receptors, Dopamine D2 / chemistry
  • Receptors, Dopamine D2 / metabolism
  • Tandem Mass Spectrometry
  • Tyramine / analogs & derivatives*
  • Tyramine / blood
  • Tyramine / pharmacokinetics
  • Tyramine / urine
  • Young Adult


  • Dopamine Agonists
  • Receptors, Dopamine D2
  • hordenine
  • Tyramine