2. Academic Validation
  3. In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements

In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements

  • Nutrients. 2024 May 22;16(11):1567. doi: 10.3390/nu16111567.
Nicole E T Pinckaers 1 2,  W Matthijs Blankesteijn 1 3,  Anastasiya Mircheva 1,  Xiao Shi 4 5,  Antoon Opperhuizen 1 6,  Frederik-Jan van Schooten 1 2,  Misha F Vrolijk 1 2
Affiliations

Affiliations

  • 1 Department of Pharmacology and Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands.
  • 2 Research Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
  • 3 School for Cardiovascular Diseases (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands.
  • 4 Research Service, Veterans Affairs Portland Health Care System, Portland, OR 97239, USA.
  • 5 Department of Psychiatry, Oregon Health and Science University, Portland, OR 97239, USA.
  • 6 Office for Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority, 3540 AA Utrecht, The Netherlands.
PMID: 38892500 DOI: 10.3390/nu16111567
Abstract

Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements. Although the health effects of these analogues are not well understood yet, they are hypothesised to be agonists of adrenergic (ADR) and trace amine-associated receptors (TAARs). Therefore, we aimed to pharmacologically characterise these compounds by investigating their activating properties of ADRs and TAAR1 in vitro. The potency and efficacy of the selected PEAs and AAs was studied by using cell lines overexpressing human ADRα1A/α1B/α1D/α2a/α2B/β1/β2 or TAAR1. Concentration-response relationships are expressed as percentages of the maximal signal obtained by the full ADR agonist adrenaline or the full TAAR1 agonist phenethylamine. Multiple PEAs activated ADRs (EC50 = 34 nM-690 µM; Emax = 8-105%). Almost all PEAs activated TAAR1 (EC50 = 1.8-92 µM; Emax = 40-104%). Our results reveal the pharmacological profile of PEAs and AAs that are often used in food supplements. Several PEAs have strong agonistic properties on multiple receptors and resemble potencies of the endogenous ligands, indicating that they might further stimulate the already activated sympathetic nervous system in exercising athletes via multiple mechanisms. The use of supplements containing one, or a combination of, PEA(s) may pose a health risk for their consumers.

Keywords

adrenaline; adrenergic receptors; alkylamine analogues; food supplements; phenethylamine analogues; trace amine-associated receptor 1.

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