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Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements
Author(s) -
Liu Yitong,
Santillo Michael F.
Publication year - 2015
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.1863
Subject(s) - cyp3a4 , pharmacology , cyp2d6 , chemistry , enzyme , cytochrome p450 , cyp1a2 , drug , dietary supplement , in vivo , biochemistry , medicine , biology , food science , microbiology and biotechnology
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 ( IC 50 = 0.14 ± 0.01 μM) and N ‐benzylphenethylamine ( IC 50 = 0.7 ± 0.2 μM), followed by several other relatively strong inhibitors ( IC 50 , 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.