N-Methyltyramine, a Gastrin-releasing Factor in Beer, and Structurally Related Compounds as Agonists for Human Trace Amine-associated Receptor 1

抄録

N-Methyltyramine (N-MeTA) is known as a gastrin-releasing factor in beer. In this study, the agonistic actions of N-MeTA as well as tyramine (TA)/β-phenylethylamine (PEA) and their other N-methylated derivatives were examined to elucidate their structure-activity relationships, using a secreted placental alkaline phosphatase (SEAP)-based reporter assay in HEK-293 cells transiently expressing a G protein-coupled receptor, human trace amine-associated receptor 1 (hTAAR1). We detected the agonistic actions of six test compounds, including N-MeTA (EC₅₀ = 6.78 µM), on hTAAR1. The agonistic actions were reduced depending on the number of N-methyl groups introduced into TA and PEA; the order of potency is PEA > N-methylphenylethylamine > TA ≈ N,N-dimethylphenylethylamine ≥ N-MeTA ≥ N,N-dimethyltyramine. Taken together with our previous study on TA/PEA as agonists for hTAAR1 in the stomach, this finding suggests that hTAAR1 might be the primary target of N-MeTA in the stomach; however, the agonistic potency of N-MeTA is weaker compared to TA and PEA.