Potential Cardiovascular Risks of Phenethylamine Analogues in Food Supplements: Evidence from Vasocontraction of Rat Artery Segments

Phenethylamine (PEA) and alkylamine (AA) analogues are frequently present in pre-workout food supplements and share structural similarity with amphetamine and the endogenous catecholamines (nor)adrenaline and dopamine, suggesting potential sympathomimetic activity. The present study investigated the vasoactive properties of PEA and AA analogues in isolated Wistar Kyoto rat mesenteric arteries, renal arteries and aorta. Our findings provide evidence that several analogues induced concentration-dependent contraction of isolated blood vessels, with potency (EC50) values ranging from 0.906 µM to 550 µM. p-Synephrine and p-octopamine were the only two substances that induced contraction of the mesenteric artery segments, whereas 6 out of 12 PEA analogues, including p-synephrine, p-octopamine, halostachine, β-methylphenethylamine, phenethylamine and dimethylphenethylamine, induced contraction of aorta and renal artery segments. These effects were largely attenuated by the α1-adrenergic receptor (ADR) antagonist prazosin, implicating ADRα1 involvement, while partial modulation by the trace amine associated receptor 1. The demonstrated vasocontractility of these compounds highlights the potential influence on the vascular tone and blood pressure regulation and the deleterious consequences for cardiovascular health in humans. These risks may be particularly pronounced in exercising individuals that have an already activated sympathetic nervous system or those with underlying Cardiovascular Disease.

Aorta; Food supplements; Mesenteric artery; Phenethylamines; Renal artery; Vasocontractility.