title: Inhibition of monoamine oxidase (MAO) by α-ethylphenethylamine  and N,α-diethylphenethylamine, two compounds related to  dietary supplements.
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 (Ki = 14.0 µM), which was 17-fold stronger compared to MAO B (Ki = 234 µM). Furthermore, N,α-DEPEA was a weak inhibitor of both MAO A (Ki = 251 µM) and MAO B (Ki = 159 µM). Trends regarding MAO A inhibition were explored among structural analogs, yielding the following ranking: amphetamine (Ki = 5.3 µM), AEPEA (Ki = 14.0 µM), methamphetamine (Ki = 17.2 µM), phentermine (Ki = 196 µM), and N,α-DEPEA (Ki = 251 µM). This study provides important data relating chemical structures and biochemical effects for two emerging compounds associated with dietary supplements.
authors.affiliation: 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. michael.santillo@fda.hhs.gov
authors.forename: Michael F
authors.initials: MF
authors.lastname: Santillo
mesh_terms: D000465:Algorithms; D002082:Butylamines / Q000009:adverse effects* / Q000032:analysis; D019587:Dietary Supplements / Q000009:adverse effects* / Q000032:analysis*; D006801:Humans; D007700:Kinetics; D008694:Methamphetamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000009:adverse effects* / Q000032:analysis*; D013329:Structure-Activity Relationship
chemical_list: D002082:Butylamines; D008996:Monoamine Oxidase Inhibitors; C587790:N,alpha-diethylphenylethylamine; D010627:Phenethylamines; C000599731:alpha-ethylphenethylamine; D008694:Methamphetamine; D008995:Monoamine Oxidase