In vitro metabolism and pharmacokinetic studies on methylone

Drug Metabolism and Disposition

Volumn 41, Issue 6, 2013, Pages 1247-1255

  Pedersen, Anders Just ^a   Petersen, Trine Hedebrink ^b   Linnet, Kristian ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE OXIDASE (FLAVIN CONTAINING); AMINOKETONE; CYTOCHROME P450 1A2; CYTOCHROME P450 2A6; CYTOCHROME P450 2B6; CYTOCHROME P450 2C18; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2D6; CYTOCHROME P450 2E1; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DIHYDROMETHYLONE; DIHYDROXYMETHCATHINONE; DIMETHYLANILINE MONOOXYGENASE; METHCATHINONE; METHYLONE; N HYDROXYMETHYLONE; NORMETHYLONE; UNCLASSIFIED DRUG;

ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG DETERMINATION; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIMIT OF DETECTION; METABOLITE; PRIORITY JOURNAL;

ANIMALS; CENTRAL NERVOUS SYSTEM STIMULANTS; CYTOCHROME P-450 CYP2D6; ENZYME INHIBITORS; HUMANS; INSECTS; METHAMPHETAMINE; MICROSOMES, LIVER;

EID: 84878256611     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.050880     Document Type: Article

References (35)

1. Bossong MG, Van Dijk JP, and Niesink R J M (2005) Methylone and mCPP, two new drugs of abuse? Addict Biol 10:321-323.
2. Cashman JR (2005) Some distinctions between flavin-containing and cytochrome P450 monooxygenases. Biochem Biophys Res Commun 338:599-604.
3. Cawrse BM, Levine B, Jufer RA, Fowler DR, Vorce SP, Dickson AJ, and Holler JM (2012) Distribution of methylone in four postmortem cases. J Anal Toxicol 36:434-439.
4. Dagnino D and Schripsema J (2005) 1H NMR quantification in very dilute toxin solutions: application to anatoxin-a analysis. Toxicon 46:236-240.
5. Dalsgaard PW, Rasmussen BS, Müller IB, and Linnet K (2012) Toxicological screening of basic drugs in whole blood using UPLC-TOF-MS. Drug Test Anal 4:313-319.
6. De Bernardis JF, Arendsen DL, Kyncl JJ, and Kerkman DJ (1987) Conformationally defined adrenergic agents.4. 1-(aminomethyl) phthalans: synthesis and pharmacological consequences of the phthalan ring oxygen atom. J Med Chem 30:178-184.
7. Den Hollander B, Rozov S, Linden AM, Uusi-Oukari M, Ojanperä I, and Korpi ER (2013) Long-term cognitive and neurochemical effects of "bath salt" designer drugs methylone and mephedrone. Pharmacol Biochem Behav 103:501-509.
8. Edlund PO and Baranczewski P (2004) Identification of BVT.2938 metabolites by LC/MS and LC/MS/MS after in vitro incubations with liver microsomes and hepatocytes. J Pharm Biomed Anal 34:1079-1090.
9. Grothusen A, Hardt J, Bräutigam L, Lang D, and Böcker R (1996) A convenient method to discriminate between cytochrome P450 enzymes and flavin-containing monooxygenases in human liver microsomes. Arch Toxicol 71:64-71.
10. Heydari A, Yeo KR, Lennard MS, Ellis SW, Tucker GT, and Rostami-Hodjegan A (2004) Mechanism-based inactivation of CYP2D6 by methylenedioxymethamphetamine. Drug Metab Dispos 32:1213-1217.
11. Jacob P and Shulgin AT (1996), inventors, Neurobiological Technologies, Inc., assignee. Preparation of novel N-substituted-2-amino-3', 4'-methylenedioxypropiophenones as anti-depressant and antiparkinsonism agents. US Patent WO9639133. 1996 June 6.
12. Johansen SS and Hansen TM (2012) Isomers of fluoroamphetamines detected in forensic cases in Denmark. Int J Legal Med 126:541-547.
13. Kamata HT, Shima N, Zaitsu K, Kamata T, Miki A, Nishikawa M, Katagi M, and Tsuchihashi H (2006) Metabolism of the recently encountered designer drug, methylone, in humans and rats. Xenobiotica 36:709-723.
14. Kelly JP (2011) Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Drug Test Anal 3:439-453.
15. Khojasteh SC, Prabhu S, Kenny JR, Halladay JS, and Lu AY (2011) Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet 36:1-16.
16. Kovács K, Tóth AR, and Kereszty EM (2012) [A new designer drug: methylone related death (in Hungarian)]. Orv Hetil 153:271-276.
17. Kraemer T and Maurer HH (2002) Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Ther Drug Monit 24:277-289.
18. Kreth KP, Kovar KA, Schwab M, and Zanger UM (2000) Identification of the human cytochromes P450 involved in the oxidative metabolism of "Ecstasy"-related designer drugs. Biochem Pharmacol 59:1563-1571.
19. Lin LY, Di Stefano EW, Schmitz DA, Hsu L, Ellis SW, Lennard MS, Tucker GT, and Cho AK (1997) Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 25:1059-1064.
20. Maurer HH, Bickeboeller-Friedrich J, Kraemer T, and Peters FT (2000) Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs ('Ecstasy'). Toxicol Lett 112-113:133-142.
21. Meyer MR, Wilhelm J, Peters FT, and Maurer HH (2010) Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem 397:1225-1233.
22. Mueller DM and Rentsch KM (2012) Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS (n), and metabolism of 11 cathinones. Anal Bioanal Chem 402:2141-2151.
23. Pearson JM, Hargraves TL, Hair LS, Massucci CJ, Frazee CC, 3rd, Garg U, and Pietak BR (2012) Three fatal intoxications due to methylone. J Anal Toxicol 36:444-451.
24. Pedersen AJ, Reitzel LA, Johansen SS, and Linnet K (2012) In vitro metabolism studies on mephedrone and analysis of forensic cases. Drug Test Anal DOI: 10.1002/dta.1369.
25. Reitzel LA, Dalsgaard PW, Müller IB, and Cornett C (2012) Identification of ten new designer drugs by GC-MS, UPLC-QTOF-MS, and NMR as part of a police investigation of a Danish Internet company. Drug Test Anal 4:342-354.
26. Silverman RB (1998) Methods in Enzymology, Enzyme Kinetics and Mechanism, Mechanismbased Enzyme Inactivators, Part D, Academic Press, London.
27. Simonsen KW, Hermansson S, Steentoft A, and Linnet K (2010) A validated method for simultaneous screening and quantification of twenty-three benzodiazepines and metabolites plus zopiclone and zaleplone in whole blood by liquid-liquid extraction and ultraperformance liquid chromatography-tandem mass spectrometry. J Anal Toxicol 34:332-341.
28. Spiller HA, Ryan ML, Weston RG, and Jansen J (2011) Clinical experience with and analytical confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States. Clin Toxicol (Phila) 49:499-505.
29. Suzuki H, Kneller MB, Haining RL, Trager WF, and Rettie AE (2002) (+)-N-3-Benzyl-nirvanol and (-)-N-3-benzyl-phenobarbital: new potent and selective in vitro inhibitors of CYP2C19. Drug Metab Dispos 30:235-239.
30. Walsky RL and Obach RS (2003) Verification of the selectivity of (+) N-3-benzylnirvanol as a CYP2C19 inhibitor. Drug Metab Dispos 31:343.
31. Wu DF, Otton SV, Inaba T, Kalow W, and Sellers EM (1997) Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol 53:1605-1612.
32. Wu RF, Liao CX, Tomita S, Ichikawa Y, and Terada LS (2004) Porcine FAD-containing monooxygenase metabolizes lidocaine, bupivacaine and propranolol in vitro. Life Sci 75:1011-1019.
33. Yuan JJ, Yang DC, Zhang JY, Bible R, Jr, Karim A, and Findlay J W A (2002) Disposition of a specific cyclooxygenase-2 inhibitor, valdecoxib, in human. Drug Metab Dispos 30:1013-1021.
34. Zaitsu K, Katagi M, Tatsuno M, Sato T, Tsuchihashi H, and Suzuki K (2011) Recently abused beta-keto derivatives of 3, 4-methylenedioxyphenylalkylamines: a review of their metabolisms and toxicological analysis. Forensic Toxicol 29:73-84.
35. Zhang D, Zhu M, and Humphreys WG (2007) Drug Metabolism in Drug Design and Drug Development, Wiley-Interscience, Wiley, Hoboken, NJ.