Identification of cytochrome P450 enzymes involved in the metabolism of 3′,4′-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP), a designer drug, in human liver microsomes

Xenobiotica

Volumn 35, Issue 3, 2005, Pages 227-237

  Springer, D ^a   Staack, R F ^a   Paul, L D ^a   Kraemer, T ^a   Maurer, H H ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

3 ,4 Methylenedioxy pyrrolidinopropiophenone; CYP2C19; CYP2D6; Intrinsic clearance; MDPPP

Indexed keywords

3',4' DIHYDROXYPYRROLIDINOPROPIOPHENONE; 3',4' METHYLENEDIOXY ALPHA PYRROLIDINOPROPIOPHENONE; COMPLEMENTARY DNA; CYTOCHROME P450; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; DESIGNER DRUG; DRUG METABOLITE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DEMETHYLATION; DRUG METABOLISM; ENZYME ISOLATION; ENZYME KINETICS; ENZYME LOCALIZATION; ENZYME MECHANISM; HUMAN; HUMAN TISSUE; ION MONITORING; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; PROTEIN EXPRESSION;

CELLS, CULTURED; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME ACTIVATION; HUMANS; KINETICS; METABOLIC CLEARANCE RATE; MICROSOMES, LIVER; PIPERIDINES;

EID: 20144386490     PISSN: 00498254     EISSN: None     Source Type: Journal    
DOI: 10.1080/00498250400028239     Document Type: Article

References (26)

1. Bertilsson L. 1995. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clinical Pharmacokinetics 29:192-209.
2. Bourrie M, Meunier V, Berger Y, Fabre G. 1996. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. Journal of Pharmacology and Experimental Therapeutics 277:321-332.
3. Bryant SG, Guernsey BG, Ingrim NB. 1983. Review of bupropion. Clinical Pharmacology 2:525-537.
4. Clarke SE. 1998. In vitro assessment of human cytochrome P450. Xenobiotica 28:1167-1202.
5. Crespi CL. 1995. Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. In: Testa B, Meyer UA, editors. Advances in Drug Research. London: Academic Press, pp 179-235.
6. Crespi CL, Miller VP. 1999. The use of heterologously expressed drug metabolizing enzymes-state of the art and prospects for the future. Pharmacology Therapeutics 84:121-131.
7. Crespi CL, Penman BW. 1997. Use of cDNA-expressed human cytochrome P450 enzymes to study potential drug-drug interactions. Advances in Pharmacology 43:171-188.
8. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE. 1992. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. British Journal of Clinical Pharmacology 34:262-265.
9. Evans WE, McLeod HL. 2003. Pharmacogenomics-drug disposition, drug targets, and side effects. New England Journal of Medicine 348:538-549.
10. Glennon RA, Yousif M, Naiman N, Kalix P. 1987. Methcathinone: a new and potent amphetamine-like agent. Pharmacology and Biochemistry Behaviour 26:547-551.
11. Guengerich FP, Parikh A, Yun CH, Kim D, Nakamura K, Motley LM, Gillam EM. 2000. What makes P450s work? Searches for answers with known and new P450s. Drug Metabolism Review 32:267-281.
12. Kalix, P, Glennon RA. 1986. Further evidence for an amphetamine-like mechanism of action of the alkaloid cathinone. Biochemical Pharmacology 35:3015-3019.
13. Kraemer T, Maurer HH. 2002. Toxicokinetics of amphetamines: Metabolism and toxicokinetic data of designer drugs, of amphetamine, methamphetamine and their N-alkyl derivatives [review]. Therapeutic Drug Monitoring 24:277-289.
14. Martinez M, Mercado O, Santamaria A, Galvan S, Vazquez M, Bucio V, Hall C, Hernandez R, Hurtazo A, Pego E, Rodriguez F, Salvatierra R, Sosa A, Rios C. 1998. The action of amfepramone on neurochemical and behavioral markers in rats. Proceedings of the Western Pharmacology Society 41:125-127.
15. Maurer HH, Kratzsch C, Weber AA, Peters FT, Kraemer T. 2002. Validated assay for quantification of oxcarbazepine and its active dihydro metabolite 10-hydroxy carbazepine in plasma by atmospheric pressure chemical ionization liquid chromatography/mass spectrometry. Journal of Mass Spectrometry 37:687-692.
16. Newton DJ, Wang RW, Lu AY. 1995. Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metabolism and Disposition 23:154-158.
17. Nichols DE. 1986. Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. Journal of Psychoactive Drugs 18:305-313.
18. Rodrigues AD. 1999. Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA-expressed cytochromes P450 and native human liver microsomes. Biochemical Pharmacology 57:465-480.
19. Roesner P, Junge T, Fritschi G, Klein B, Thielert K, Kozlowski M. 1999. Neue synthetische Drogen: piperazin-, procyclidin- und alpha- aminopropiophenonderivate. Toxichem und Krimtech. 66:81-90.
20. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. 1994. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. Journal of Pharmacology and Experimental Therapy 270:414-423.
21. Smith DA, Abel SM, Hyland R, Jones BC. 1998. Human cytochrome P450s: selectivity and measurement in vivo. Xenobiotica 28:1095-1128.
22. Springer D, Fritschi G, Maurer HH. 2003a. Metabolism and toxicological detection of the new designer drug 4′-methoxy-a-pyrrolidinopropiophenone studied in rat urine using gas chromatography-mass spectrometry. Journal of Chromatography B Analytical Technology Biomedical Life Science 793:331-342.
23. Springer D, Paul LD, Staack RF, Kraemer T, Maurer HH. 2003b. Identification of the cytochrome P450 enzymes involved in the metabolism of 4′-methyl-(alpha)-pyrrolidinopropiophenone, a novel scheduled designer drug, in human liver microsomes. Drug Metabolism Disposition 31:979-982.
24. Springer D, Staack RF, Paul LD, Kraemer T, Maurer HH. 2003c. Identification of cytochrome P450 enzymes involved in the metabolism of 4′-methoxy-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomes. Xenobiotica 33:989-998.
25. Stormer E, Von Moltke LL, Shader RI, Greenblatt DJ. 2000. Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metabolism and Disposition 28:1168-1175.
26. Venkatakrishnan K, Von Moltke LL, Court MH, Harmatz JS, Crespi CL, Greenblatt DJ. 2000. Comparison between cytochrome P450 (CYP) content and relative activity approaches to scaling from cDNA-expressed CYPs to human liver microsomes: ratios of accessory proteins as sources of discrepancies between the approaches. Drug Metabolism and Disposition 28:1493-1504.