Phenethylamines in pre-workout supplements alter arterial pressure, heart rate, and body temperature in rats

  • Eur J Pharmacol. 2026 Jun 10:1026:178966. doi: 10.1016/j.ejphar.2026.178966.
Nicole E T Pinckaers  1 ,  W Matthijs Blankesteijn  2 ,  Rachelle Peeters  3 ,  Petra Dijkstra  3 ,  Rik Tinnemans  3 ,  Antoon Opperhuizen  4 ,  Frederik-Jan van Schooten  5 ,  Misha Vrolijk  5
Affiliations
  • 1. Department of Pharmacology and Toxicology, Maastricht University, the Netherlands; Research Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, the Netherlands. Electronic address: [email protected].
  • 2. Department of Pharmacology and Toxicology, Maastricht University, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands.
  • 3. Central Animal Testing Facilities (CPV), Maastricht University, the Netherlands.
  • 4. Department of Pharmacology and Toxicology, Maastricht University, the Netherlands; Office for Risk Assessment and Research, Netherlands Food and Consumer Product Safety Authority (NVWA), the Netherlands.
  • 5. Department of Pharmacology and Toxicology, Maastricht University, the Netherlands; Research Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, the Netherlands.
PMID: 42128191 DOI: 10.1016/j.ejphar.2026.178966
Abstract

Phenethylamine (PEA) and its analogues are frequently present in pre-workout and weight loss food supplements and share structural similarity with amphetamine and the endogenous catecholamines (nor)adrenaline and dopamine, suggesting potential sympathomimetic activity. Multiple adverse cardiovascular events have been associated with the use of food supplements containing these ingredients, while knowledge of the underlying pharmacology and toxicology of such food supplements and their ingredients remains limited. Therefore, the aim of the current study was to investigate the acute cardiovascular effects of a selection of PEAs in conscious rats. Heart rate (HR), arterial pressure (AP) and body temperature were continuously, and wirelessly, monitored using pressure telemetry in Wistar-Kyoto rats that were intravenously exposed to cumulative doses of PEA and seven commonly used analogues: BMPEA, halostachine, higenamine, isopropyloctopamine, p-octopamine, p-synephrine and p-tyramine. All PEAs, except PEA itself and BMPEA, significantly altered AP with maximal absolute increases between 65 and 103 mmHg. Maximal absolute increases in HR induced by higenamine and isopropyloctopamine were found to be 110 and 123 beats per minute, respectively. The PEA analogues BMPEA, p-octopamine, halostachine and p-synephrine, instantly lead to reduced body temperatures, ranging from minus 0.5 to minus 1.5 °C. This study demonstrates that several PEAs, exert pronounced and rapid effects on AP, HR and body temperature in rats. The magnitudes of these effects were similar to or even higher than the cardiovascular changes induced by adrenaline, suggesting that combining these substances with physical exercise may amplify sympathetic load and pose a serious health risk, particularly for individuals with underlying cardiovascular vulnerabilities.

Keywords
Adrenaline; Blood pressure; Body temperature; Food supplements; Heart rate; Phenethylamines; Rats.
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