Identification of cytochrome p450 enzymes involved in the metabolism of 4′-methyl-α-pyrrolidinopropiophenone, a novel scheduled designer drug, in human liver microsomes

Drug Metabolism and Disposition

Volumn 31, Issue 8, 2003, Pages 979-982

  Springer, Dietmar ^a   Paul, Liane D ^a   Staack, Roland F ^a   Kraemer, Thomas ^a   Maurer, Hans H ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

4' METHYL ALPHA PYRROLIDINOPROPIOPHENONE; CYTOCHROME P450; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; DESIGNER DRUG; PROPIOPHENONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BIOTRANSFORMATION; CATALYSIS; CONTROLLED STUDY; HUMAN; HYDROXYLATION; KINETICS; LIVER METABOLISM; LIVER MICROSOME; NONHUMAN; PRIORITY JOURNAL; TOXICOKINETICS;

ANIMALS; BACULOVIRIDAE; CHROMATOGRAPHY, LIQUID; CYTOCHROME P-450 CYP2D6; DESIGNER DRUGS; HUMANS; HYDROXYLATION; KINETICS; MASS SPECTROMETRY; MICROSOMES, LIVER; PROPIOPHENONES; PYRROLES;

INSECTA; RATTUS NORVEGICUS; UNIDENTIFIED BACULOVIRUS;

EID: 0042025298     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.31.8.979     Document Type: Article

References (18)

1. Bertilsson L (1995) Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 29:192-209.
2. Bryant SG, Guernsey BG, and Ingrim NB (1983) Review of bupropion. Clin Pharm 2:525-537.
3. Clarke SE (1998) In vitro assessment of human cytochrome P450. Xenobiotica 28:1167-1202.
4. Crespi CL and Miller VP (1999) The use of heterologously expressed drug metabolizing enzymes-state of the art and prospects for the future. Pharmacol Ther 84:121-131.
5. Glennon RA, Yousif M, Naiman N, and Kalix P (1987) Metheathinone: a new and potent amphetamine-like agent. Pharmacol Biochem Behav 26:547-551.
6. Hutzler JM and Tracy TS (2002) Atypical kinetic profiles in drug metabolism reactions. Drug Metab Dispos 30:355-362.
7. Inouye K, Mizokawa T, Saito A, Tonomura B, and Ohkawa H (2000) Biphasic kinetic behavior of rat cytochrome P-4501A1-dependent monooxygenation in recombinant yeast microsomes. Biochim Biophys Acta 1481:265-272.
8. Kalix P and Glennon RA (1986) Further evidence for an amphetamine-like mechanism of action of the alkaloid cathinone. Biochem Pharmacol 35:3015-3019.
9. Korzekwa KR, Krishnamachary N, Shou M, Ogai A, Parise RA, Rettie AE, Gonzalez FJ, and Tracy TS (1998) Evaluation of atypical cytochrome P450 kinetics with two-substrate models: evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry 37:4137-4147.
10. 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, and Rios C (1998) The action of amfepramone on neurochemical and behavioral markers in rats. Proc West Pharmacol Soc 41:125-127.
11. Maurer HH, Kratzsch C, Weber AA, Peters FT, and Kraemer T (2002) Validated assay for quantification of oxcarbazepine and its active dihydro metabolite 10hydroxy carbazepine in plasma by atmospheric pressure chemical ionization liquid chromatography/mass spectrometry. J Mass Spectrom 37:687-692.
12. Miller GP and Guengerich FP (2001) Binding and oxidation of alkyl 4-nitrophenyl ethers by rabbit cytochrome P450 1A2: evidence for two binding sites. Biochemistry 40:7262-7272.
13. Oda Y and Kharasch ED (2001) Metabolism of levo-alpha-Acetylmethadol (LAAM) by human liver cytochrome P450: involvement of CYP3A4 characterized by atypical kinetics with two binding sites. J Pharmacol Exp Ther 297:410-422.
14. Roesner P, Junge T, Fritschi G, Klein B, Thielert K, and Kozlowski M (1999) Neue synthetische Drogen: Piperazin-. Procyclidin- und alpha-Aminopropiophenonderivate. Toxichem Krimtech 66:81-90.
15. Smith DA, Abel SM, Hyland R, and Jones BC (1998) Human cytochrome P450s: selectivity and measurement in vivo. Xenobiotica 28:1095-1128.
16. Springer D, Peters FT, Fritschi G, and Maurer HH (2002) Studies on the metabolism and toxicological detection of the new designer drug 4′-methyl-alpha-pyrrolidinopropiophenone (MPPP) in urine using gas chromatography-mass spectrometry. J Chromatogr B 773:25-33.
17. Stormer E, von Moltke LL, and Greenblatt DJ (2000) Scaling drug biotransformation data from cDNA-expressed cytochrome P-450 to human liver: a comparison of relative activity factors and human liver abundance in studies of mirtazapine metabolism. J Pharmacol Exp Ther 295:793-801.
18. Venkatakrishnan K, von Moltke LL, Court MH, Harmatz JS, Crespi CL, and 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 Metab Dispos 28:1493-1504.