Pharmacological profiles of compounds in preworkout supplements (“boosters”)

Abstract

Preworkout supplements (“boosters”) are used to enhance physical and mental performance during workouts. These products may contain various chemical substances with undefined pharmacological activity. We investigated whether substances that are contained in commercially available athletic multiple-ingredient preworkout supplements exert amphetamine-type activity at norepinephrine, dopamine, and serotonin transporters (NET, DAT, and SERT, respectively). We assessed the in vitro monoamine transporter inhibition potencies of the substances using human embryonic kidney 293 cells that expressed the human NET, DAT, and SERT. The phenethylamines β-phenethylamine, N-methylphenethylamine, β-methylphenethylamine, N-benzylphenethylamine, N-methyl-β-methylphenethylamine, and methylsynephrine inhibited the NET and less potently the DAT similarly to D-amphetamine. β-phenethylamine was the most potent, with IC50 values of 0.05 and 1.8 μM at the NET and DAT, respectively. These IC50 values were comparable to D-amphetamine (IC50 = 0.09 and 1.3 μM, respectively). The alkylamines 1,3-dimethylbutylamine and 1,3-dimethylamylamine blocked the NET but not the DAT. Most of the phenethylamines interacted with trace amine-associated receptor 1, serotonin 5-hydroxytryptamine-1A receptor, and adrenergic α1A and α2A receptors at submicromolar concentrations. None of the compounds blocked the SERT. In conclusion, products that are used by athletes may contain substances with mainly noradrenergic amphetamine-type properties.