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

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.