Monitoring of the dopamine D2 receptor agonists hordenine and N-methyltyramine during the brewing process and in commercial beer samples

Food Chem. 2019 Mar 15;276:745-753. doi: 10.1016/j.foodchem.2018.10.067. Epub 2018 Oct 13.


The phenethylamine alkaloid hordenine, present in germinated barley, was identified recently as a functionally selective dopamine D2 receptor agonist contributing potentially to the rewarding effects of drinking beer. Here, it was shown that the hordenine precursor N-methyltyramine binds with a similar affinity to the dopamine D2 receptor as hordenine (Ki 31.3 µM) showing also selectivity towards the G protein-mediated pathway over the β-arrestin pathway. Using a newly developed UHPLC-ESI-MS/MS method to monitor beer production, we demonstrated that hordenine and N-methyltyramine were released continuously from barley malt during mashing and were stable during fermentation and conditioning. The amounts released from different base malt types were in a similar range but tended to be higher from caramel malts. Hordenine and N-methyltyramine concentrations in 24 types of beer varied between 1.05-6.32 and 0.59-4.61 mg/L, respectively. Thus, the human uptake of the alkaloids during beer consumption is in the low milligram range.

Keywords: Beer; Brewing; Dopamine D2 receptor agonist; Fermentation; Hordenine; Mashing; N-Methyltyramine.

MeSH terms

  • Animals
  • Beer / analysis*
  • CHO Cells
  • Chromatography, High Pressure Liquid
  • Cricetulus
  • Dopamine Agonists / analysis*
  • Dopamine Agonists / metabolism
  • Fermentation
  • Food Analysis / methods
  • Hordeum / metabolism
  • Humans
  • Radioligand Assay
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry
  • Tyramine / analogs & derivatives*
  • Tyramine / analysis
  • Tyramine / metabolism


  • DRD2 protein, human
  • Dopamine Agonists
  • Receptors, Dopamine D2
  • methyl-4-tyramine
  • hordenine
  • Tyramine