title: Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements.
abstract: A number of dietary supplements used for weight loss and athletic performance enhancement have been recently shown to contain a variety of stimulants, for which there is a lack of pharmacological and toxicological information. One concern for these emerging compounds is their potential to inhibit metabolic enzymes in the liver such as cytochromes P450 (CYP), which can lead to unexpected interactions among dietary supplements, drugs, and other xenobiotics. In this study, inhibition of human recombinant CYP2D6 and CYP3A4 by 27 amine stimulants associated with dietary supplements and their analogs was evaluated by luminescence assays. The strongest CYP2D6 inhibitors were coclaurine (IC50  = 0.14 ± 0.01 μM) and N-benzylphenethylamine (IC50  = 0.7 ± 0.2 μM), followed by several other relatively strong inhibitors (IC50 , 2-12 μM) including β-methylphenethylamine, N,β-dimethylphenethylamine (phenpromethamine), 1,3-dimethylamylamine (DMAA), N,α-diethylphenethylamine, higenamine (norcoclaurine) and N,N-diethylphenethylamine. Only nine compounds inhibited CYP3A4 by 20-55% at 100 μM. Results of this study illustrate that several amine stimulants associated with dietary supplements inhibit CYP2D6 and CYP3A4 in vitro, and these compounds may participate in adverse drug-dietary supplement interactions in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, 8301 Muirkirk Rd, Laurel, MD, 20708, USA.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, 8301 Muirkirk Rd, Laurel, MD, 20708, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Santillo
mesh_terms: D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects*; D051544:Cytochrome P-450 CYP3A / Q000009:adverse effects*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019587:Dietary Supplements; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50
chemical_list: D000588:Amines; D000697:Central Nervous System Stimulants; D065607:Cytochrome P-450 Enzyme Inhibitors; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: CYP2D6; CYP3A4; dietary supplements; enzyme inhibition; stimulants