Scientific Publications by FDA Staff

Food Chem Toxicol 2014 Oct 16;74:265-9

Inhibition of monoamine oxidase (MAO) by alpha-ethylphenethylamine and N,alpha-diethylphenethylamine, two compounds related to dietary supplements.

Santillo MF

Phenethylamines can interact with the metabolic enzyme monoamine oxidase (MAO), which can cause neurochemical dysfunction or changes in drug potency. A methamphetamine analog, N,alpha-diethylphenethylamine (N,alpha-DEPEA), was recently discovered in athletic performance-enhancing supplements, along with discovery of its metabolite, alpha-ethylphenethylamine (AEPEA). In vitro inhibition of human recombinant MAO by AEPEA and N,alpha-DEPEA was evaluated by measuring the fluorescence of 4-hydroxyquinoline produced from MAO substrate, kynuramine. AEPEA competitively inhibited human recombinant MAO A (Ki = 14.0 microM), which was 17-fold stronger compared to MAO B (Ki = 234 microM). Furthermore, N,alpha-DEPEA was a weak inhibitor of both MAO A (Ki = 251 microM) and MAO B (Ki = 159 microM). Trends regarding MAO A inhibition were explored among structural analogs, yielding the following ranking: amphetamine (Ki = 5.3 microM), AEPEA (Ki = 14.0 microM), methamphetamine (Ki = 17.2 microM), phentermine (Ki = 196 microM), and N,alpha-DEPEA (Ki = 251 microM). This study provides important data relating chemical structures and biochemical effects for two emerging compounds associated with dietary supplements.