Food and Chemical Toxicology

Volume 74, December 2014, Pages 265–269

Short communication

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

• Michael F. Santillo^,

doi:10.1016/j.fct.2014.10.009

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Highlights

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AEPEA was a stronger MAO A inhibitor (K_i = 14.0 µM) vs. N,α-DEPEA (K_i = 251 µM).

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AEPEA and N,α-DEPEA were weak MAO B inhibitors (K_i > 159 µM).

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K_i for MAO A: amphetamine < AEPEA ≈ methamphetamine < phentermine < N,α-DEPEA.

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Abstract

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

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Graphical Abstract

Abbreviations

• AEPEA, α-ethylphenethylamine;
• N,α-DEPEA, N,α-diethylphenethylamine;
• MAO, monoamine oxidase;
• SEM, standard error of the mean

Keywords

• Monoamine oxidase (MAO);
• N-ethyl-1-phenyl-2-butanamine;
• 1-phenyl-2-butanamine;
• Enzyme inhibition;
• Amphetamines;
• Diethylphenethylamines

Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, 8301 Muirkirk Road, Laurel, MD 20708, USA. Tel.: +1 301 796 0564.

Published by Elsevier Ltd.