Abstract

Dietary supplements often contain additives not listed on the label, including a-ethyl homologs of amphetamine such as N,a-diethylphenethylamine (DEPEA). Here we examined the neurochemical and cardiovascular effects of a-ethylphenethylamine (AEPEA), N-methyl-a-ethylphenethylamine (MEPEA), and DEPEA as compared to the effects of amphetamine. All drugs were tested in vitro using uptake inhibition and release assays for monoamine transporters. As expected, amphetamine acted as a potent and efficacious releasing agent at dopamine transporters (DAT) and norepinephrine transporters (NET) in vitro. AEPEA and MEPEA were also releasers at catecholamine transporters, with greater potency at NET than DAT. DEPEA displayed fully efficacious release at NET but weak partial release at DAT (i.e., 40% of maximal effect). In freely moving, conscious male rats fitted with biotelemetry transmitters for physiological monitoring, amphetamine (0.1-3.0 mg/kg, sc) produced robust dose-related increases in blood pressure (BP), heart rate (HR), and motor activity. AEPEA (1-10 mg/kg, sc) produced significant increases in BP but not HR or activity, whereas DEPEA and MEPEA (1-10 mg/kg, sc) increased BP, HR, and activity. In general, the phenethylamine analogs were approximately 10-fold less potent than amphetamine. Our results show that a-ethylphenethylamine analogs are biologically active. While less potent than amphetamine, they produce cardiovascular effects that could pose risks to humans. Given that MEPEA and DEPEA increased locomotor activity, these substances may also have significant abuse potential.

Significance Statement The a-ethyl homologs of amphetamine have significant cardiovascular, behavioral and neurochemical effects in rats. Given that these compounds are often not listed on the ingredient label of dietary supplements, these compounds could pose a risk to humans using these products.