TY - JOUR T1 - The supplement adulterant β-methylphenethylamine (BMPEA, 2-phenylpropan-1-amine) increases blood pressure by acting at peripheral norepinephrine transporters JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.118.255976 SP - jpet.118.255976 AU - Charles W Schindler AU - Eric C Thorndike AU - Kenner C Rice AU - John S Partilla AU - Michael H Baumann Y1 - 2019/01/01 UR - http://jpet.aspetjournals.org/content/early/2019/03/21/jpet.118.255976.abstract N2 - β-Methylphenethylamine (BMPEA, 2-phenylpropan-1-amine) is a structural isomer of amphetamine (1-phenylpropan-2-amine) that has been identified in pre-workout and weight loss supplements, yet little information is available about its pharmacology. Here, the neurochemical and cardiovascular effects of BMPEA and its analogs, N-methyl-2-phenylpropan-1-amine (MPPA) and N,N-dimethyl-2-phenylpropan-1-amine (DMPPA), were compared to structurally-related amphetamines. As expected, amphetamine and methamphetamine were potent substrate-type releasing agents at transporters for dopamine (DAT) and norepinephrine (NET) in rat brain synaptosomes. BMPEA and MPPA were also substrates at DAT and NET but they were at least 10-fold less potent than amphetamine. DMPPA was a weak substrate only at NET. Importantly, the releasing actions of BMPEA and MPPA were more potent at NET than DAT. Amphetamine produced significant dose-related increases in blood pressure (BP), heart rate (HR), and locomotor activity in conscious rats fitted with surgically-implanted biotelemetry transmitters. BMPEA, MPPA and DMPPA produced increases in BP that were similar to the effects of amphetamine, but the compounds failed to substantially affect HR or activity. The hypertensive effect of BMPEA was reversed by the α-adrenergic antagonist prazosin but not the ganglionic blocker chlorisondamine. Radioligand binding at various G protein-coupled receptors did not identify non-transporter sites of action which could account for cardiovascular effects of BMPEA or its analogs. Our results show that BMPEA, MPPA and DMPPA are biologically active. The compounds are unlikely to be abused due to weak effects at DAT, but they could produce adverse cardiovascular effects via substrate activity at peripheral NET sites. ER -