Cytochrome P450 2D6 and 3A4 enzyme inhibition by amine stimulants in dietary supplements

Drug Testing and Analysis

Volumn 8, Issue 3-4, 2016, Pages 307-310

  Liu, Yitong ^a   Santillo, Michael F ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

Dietary supplements; Enzyme inhibition; Stimulants

Indexed keywords

BIOCHEMISTRY; DRUG INTERACTIONS; ENZYME INHIBITION; FOOD ADDITIVES; NUTRITION; VITAMINS;

ATHLETIC PERFORMANCE; CYTOCHROMES P450; HIGENAMINE; IN-VITRO; LOSS PERFORMANCE; LUMINESCENCE ASSAY; METABOLIC ENZYMES; PERFORMANCE ENHANCEMENTS; STIMULANT; WEIGHT LOSS;

DIETARY SUPPLEMENTS;

4 METHYL 2 HEXYLAMINE; AMINE; BETA METHYLPHENETHYLAMINE; COCLAURINE; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; HIGENAMINE; N ALPHA DIETHYLPHENETHYLAMINE; N BENZYLPHENETHYLAMINE; N BETA DIMETHYLPHENETHYLAMINE; N,N DIETHYLPHENETHYLAMINE; PHENPROMETHAMINE; UNCLASSIFIED DRUG; CENTRAL STIMULANT AGENT; CYP3A4 PROTEIN, HUMAN; CYTOCHROME P450 3A; CYTOCHROME P450 INHIBITOR;

ARTICLE; CONTROLLED STUDY; DIET SUPPLEMENTATION; DRUG DETERMINATION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; IN VITRO STUDY; LUMINESCENCE; MOLECULAR DYNAMICS; PRIORITY JOURNAL; DIETARY SUPPLEMENT; DRUG EFFECTS; HUMAN; IC50;

AMINES; CENTRAL NERVOUS SYSTEM STIMULANTS; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME INHIBITORS; DIETARY SUPPLEMENTS; HUMANS; IN VITRO TECHNIQUES; INHIBITORY CONCENTRATION 50;

EID: 84941299660     PISSN: 19427603     EISSN: 19427611     Source Type: Journal    
DOI: 10.1002/dta.1863     Document Type: Article

References (26)

1. Y. Zhang, R. M. Woods, Z. S. Breitbach, D. W. Armstrong . 1, 3-Dimethylamylamine (DMAA) in supplements and geranium products: natural or synthetic? Drug Test. Anal. 2012, 4, 986.
2. P.A. Cohen, C. Bloszies, C. Yee, R. Gerona . An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements. Drug Test. Anal. 2015. DOI:10.1002/dta.1793.
3. S. R. Lee, J. M. Schriefer, T. A. Gunnels, I. C. Harvey, R. J. Bloomer . Acute oral intake of a higenamine-based dietary supplement increases circulating free fatty acids and energy expenditure in human subjects. Lipids Health Dis. 2013, 12, 148.
4. J. R. Docherty . Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Br. J. Pharmacol. 2008, 154, 606.
5. Y. Liu, H. Hao, C. Liu, G. Wang, H. Xie . Drugs as CYP3A probes, inducers, and inhibitors. Drug Metab. Rev. 2007, 39, 699.
6. K. R. Crews, A. Gaedigk, H. M. Dunnenberger, J. S. Leeder, T. E. Klein, K. E. Caudle, C. E. Haidar, D. D. Shen, J. T. Callaghan, S. Sadhasivam, C. A. Prows, E. D. Kharasch, T. C. Skaar . Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin. Pharmacol. Ther. 2014, 95, 376.
7. B. J. Gurley, A. Swain, M. A. Hubbard, D. K. Williams, G. Barone, F. Hartsfield, Y. Tong, D. J. Carrier, S. Cheboyina, S. K. Battu . Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol. Nutr. Food Res. 2008, 52, 755.
8. L. K. Teh, L. Bertilsson . Pharmacogenomics of CYP2D6: molecular genetics, interethnic differences and clinical importance. Drug Metab. Pharmacokinet. 2012, 27, 55.
9. J. J. Cali, D. Ma, M. Sobol, D. J. Simpson, S. Frackman, T. D. Good, W. J. Daily, D. Liu . Luminogenic cytochrome P450 assays. Expert Opin. Drug Metab. Toxicol. 2006, 2, 629.
10. P. L. Meisenheimer, H. T. Uyeda, D. Ma, M. Sobol, M. G. McDougall, C. Corona, D. Simpson, D. H. Klaubert, J. J. Cali . Proluciferin acetals as bioluminogenic substrates for cytochrome P450 activity and probes for CYP3A inhibition. Drug Metab. Dispos. 2011, 39, 2403.
11. TM Assays. Promega technical bulletin TB325. Promega Corp., Madison, WI USA, 2015.
12. N. Thorne, J. Inglese, D. S. Auld . Illuminating insights into firefly luciferase and other bioluminescent reporters used in chemical biology. Chem. Biol. 2010, 17, 646.
13. V. Michaud, J. Turgeon . Assessment of competitive and mechanism-based inhibition by clarithromycin: use of domperidone as a CYP3A probe-drug substrate and various enzymatic sources including a new cell-based assay with freshly isolated human hepatocytes. Drug Metab. Lett. 2010, 4, 69.
14. B. Venhuis, P. Keizers, A. van Riel, D. de Kaste . A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events. Drug Test. Anal. 2014, 6, 578.
15. P. A. Cohen, J. C. Travis, B. J. Venhuis . A methamphetamine analog (N, α-diethyl-phenylethylamine) identified in a mainstream dietary supplement. Drug Test. Anal. 2014, 6, 805.
16. M. F. Santillo . Inhibition of monoamine oxidase (MAO) by α-ethylphenethylamine and N, α-diethylphenethylamine, two compounds related to dietary supplements. Food Chem. Toxicol. 2014, 74, 265.
17. B. K. Schilling, K. G. Hammond, R. J. Bloomer, C. S. Presley, C. R. Yates . Physiological and pharmacokinetic effects of oral 1, 3-dimethylamylamine administration in men. BMC Pharmacol. Toxicol. 2013, 14, 52.
18. M. Carvalho, H. Carmo, V. M. Costa, J. P. Capela, H. Pontes, F. Remião, F. Carvalho, M. L. Bastos . Toxicity of amphetamines: an update. Arch. Toxicol. 2012, 86, 1167.
19. A. Douglas, J. G. Douglas, C. E. Robertson, J. F. Munro . Plasma phentermine levels, weight loss and side-effects. Int. J. Obes. 1983, 7, 591.
20. I. Kanfer, R. Dowse, V. Vuma . Pharmacokinetics of oral decongestants. Pharmacother. 1993, 13, 116S.
21. J. H. Hengstmann, W. Konen, C. Konen, M. Eichelbaum, H. J. Dengler . The physiological disposition of p-octopamine in man. Naunyn Schmiedebergs Arch. Pharmacol. 1974, 283, 93.
22. D. Wu, S. V. Otton, T. Inaba, W. Kalow, E. M. Sellers . Interactions of amphetamine analogs with human liver CYP2D6. Biochem. Pharmacol. 1997, 53, 1605.
23. L. L. von Moltke, D. J. Greenblatt, D. A. Ciraulo, J. M. Grassi, B. W. Granda, S. X. Duan, J. S. Harmatz, R. I. Shader . Appetite suppressant drugs as inhibitors of human cytochromes P450: in vitro inhibition of P450-2D6 by D- and L-fenfluramine, but not phentermine. J. Clin. Psychopharmacol. 1998, 18, 338.
24. M. V. Bach, R. T. Coutts, G. B. Baker . Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives. Xenobiotica. 1999, 29, 719.
25. L. Y. Lin, E. W. Di Stefano, D. A. Schmitz, L. Hsu, S. W. Ellis, M. S. Lennard, G. T. Tucker, A. K. Cho . Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab. Dispos. 1997, 25, 1059.
26. G. P. Miller, I. H. Hanna, Y. Nishimura, F. P. Guengerich . Oxidation of phenethylamine derivatives by cytochrome P450 2D6: the issue of substrate protonation in binding and catalysis. Biochem. 2001, 40, 14215.