Narrative cv coming soon 

Abstract: Pre-workout and weight loss agents are a popular category of food supplements among sport athletes and overweight individuals, and their use has risen significantly in recent years. These products often contain pharmacologically active compounds, including phenethylamines (PEAs), to induce promised effects. However, for most PEAs pharmacological and toxicological data are lacking, and their use may pose serious health risks. Several cases of serious cardiovascular events, such as palpitations, myocardial infarction and cardiac arrest have been linked to the use of supplements containing PEAs. Previously, we showed that multiple PEAs can activate human adrenergic receptors (ADR) and trace amine associated receptor 1 (TAAR1) in vitro, suggesting that their use may mimic the activation of the sympathetic nervous system by increasing heart rate and blood pressure. This study aims to investigate the effects of PEAs on arterial pressure, heart rate and body temperature in WKY rats. Pressure telemeters for measuring arterial pressure, heart rate and body temperature were surgically implanted in the abdominal aorta in male and female WKY rats. Measurements were taken before, during and after exposure to adrenaline and various PEAs (i.e. p-synephrine, p-octopamine, halostachine, higenamine, isopropyloctopamine, β-methylphenethylamine and phenethylamine). The compounds were administered intravenously via the jugular vein in a cumulative dosing regime. Concentration ranges were selected based on previously conducted in vitro ADR and TAAR1 activation assays and ranged from 0.3 nmol/kg to 300 µmol/kg body weight. 
Adrenaline, p-synephrine, p-octopamine and halostachine increased arterial pressure, whereas higenamine and isopropyloctopamine decreased it (Figure 1A). β-Methylphenethylamine had no effect on arterial pressure. Heart rate was decreased by adrenaline, p-synephrine, p-octopamine, halostachine and β-methylphenethylamine, while higenamine and isopropyloctopamine increased heart rate (Figure 1B). The effects on both arterial pressure and heart rate were dose-dependent. Body temperature decreased within 16 minutes after administration of the highest dose of p-synephrine, p-octopamine, halostachine and β-methylphenethylamine (Figure 1C). In contrast, body temperature was not affected by adrenaline and slightly increased by higenamine and isopropyloctopamine. Our data show that multiple PEAs affect arterial pressure, heart rate and body temperature in WKY rats in distinct ways. Compounds that increased arterial pressure also decrease heart rate and vice versa, suggesting activation of the baroreflex. These results are consistent with our previously conducted in vitro research on α1/β1 ADR and TAAR1 activation. We demonstrated that the potent β1 agonists higenamine and isopropyloctopamine increased heart rate and that the α1-agonists p-synephrine, p-octopamine and halostachine increased arterial pressure in WKY rats. In the current study, all previously confirmed TAAR1 agonists decreased body temperature, with the exception of the potent β1 agonists, which increased heart rate. These results suggest that the use of food supplements containing these PEAs may further stimulate the already activated sympathetic nervous system in exercising individuals, by increasing heart rate and blood pressure, and may therefore pose a serious health risk to consumers.