Identification of human cytochrome P450 2D6 as major enzyme involved in the O-demethylation of the designer drug p-methoxymethamphetamine

Drug Metabolism and Disposition

Volumn 32, Issue 4, 2004, Pages 379-381

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

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

4 METHOXYAMPHETAMINE; CYTOCHROME P450 2D6; DESIGNER DRUG; DRUG METABOLITE; PHOLEDRINE; QUINIDINE;

ANIMAL CELL; ARTICLE; BACULOVIRUS; CATALYSIS; COMPARATIVE STUDY; CONTROLLED STUDY; DEMETHYLATION; DRUG ABUSE; DRUG FATALITY; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME ANALYSIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; INSECT CELL; LIVER MICROSOME; MICHAELIS MENTEN KINETICS; NONHUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; TOXICOKINETICS;

AMPHETAMINES; BIOTRANSFORMATION; CHROMATOGRAPHY, LIQUID; CYTOCHROME P-450 CYP2D6; DESIGNER DRUGS; GENOTYPE; HUMANS; MASS SPECTROMETRY; METHAMPHETAMINE; METHYLATION; MICROSOMES, LIVER; MOLECULAR STRUCTURE;

ANIMALIA; INSECTA; RATTUS NORVEGICUS; UNIDENTIFIED BACULOVIRUS;

EID: 1842432478     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.32.4.379     Document Type: Article

References (22)

1. Bach MV, Coutts RT, and Baker GB (1999) Involvement of CYP2D6 in the in vitro metabolism of amphetamine, two N-alkylamphetamines and their 4-methoxylated derivatives. Xenobiotica 29:719-732.
2. Clarke SE (1998) In vitro assessment of human cytochrome P450. Xenobiotica 28:1167-1202.
3. Coutts RT, Bolaji OO, Su P, and Baker GB (1994) Metabolism of methoxyphenamine in vitro by a CYP2D6 microsomal preparation. Drug Metab Dispos 22:756-760.
4. European Communities (2002) Council decision of 28 February 2002 concerning control measures and criminal sanctions in respect of the new synthetic drug PMMA. Off J Eur Commun 45:14.
5. Felgate HE, Felgate PD, James RA, Sims DN, and Vozzo DC (1998) Recent paramethoxyamphetamine deaths. J Anal Toxicol 22:169-172.
6. Glennon RA and Higgs R (1992) Investigation of MDMA-related agents in rats trained to discriminate MDMA from saline. Pharmacol Biochem Behav 43:759-763.
7. Glennon RA, Ismaiel AE, Martin B, Poff D, and Sutton M (1988) A preliminary behavioral investigation of PMMA, the 4-methoxy analog of methamphetamine. Pharmacol Biochem Behav 31:9-13.
8. Glennon RA, Young R, Dukat M, and Cheng Y (1997) Initial characterization of PMMA as a discriminative stimulus. Pharmacol Biochem Behav 57:151-158.
9. James RA and Dinan A (1998) Hyperpyrexia associated with fatal paramethoxyamphetamine (PMA) abuse. Med Sci Law 38:83-85.
10. Johansen SS, Hansen AC, Muller IB, Lundemose JB, and Franzmann MB (2003) Three fatal cases of PMA and PMMA poisoning in Denmark. J Anal Toxicol 27:253-256.
11. Kraner JC, McCoy DJ, Evans MA, Evans LE, and Sweeney BJ (2001) Fatalities caused by the MDMA-related drug paramethoxyamphetamine (PMA). J Anal Toxicol 25:645-648.
12. Ling LH, Marchant C, Buckley NA, Prior M, and Irvine RJ (2001) Poisoning with the recreational drug paramethoxyamphetamine ("death"). Med J Aust 174:453-455.
13. Margolis JM and Obach RS (2003) Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502D6: implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metab Dispos 31:606-611.
14. Martin TL (2001) Three cases of fatal paramethoxyamphetamine overdose. J Anal Toxicol 25:649-651.
15. Rangisetty JB, Bondarev ML, Chang-Fong J, Young R, and Glennon RA (2001) PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA. Pharmacol Biochem Behav 69:261-267.
16. Shulgin A (1991) #130 PMMA, in Pihkal, A Chemical Love Story (Dan Joy ed) pp 783-785, Transform Press, Berkley, CA.
17. Springer D, Paul LD, Staack RF, Kraemer T, and Maurer HH (2003a) Identification of the cytochrome P450 enzymes involved in the metabolism of 4′-methyl-(a)-pyrrolidinopropiophenone, a novel scheduled designer drug, in human liver microsomes. Drug Metab Dispos 31:979-982.
18. Springer D, Staack RF, Paul LD, Kraemer T, and Maurer HH (2003b) 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.
19. Staack RF, Fehn J, and Maurer HH (2003) New designer drug para-methoxymethamphetamine: studies on its metabolism and toxicological detection in urine using gas chromatography-mass spectrometry. J Chromatogr Analyt Technol Biomed Life Sci 789:27-41.
20. Steele TD, Katz JL, and Ricaurte GA (1992) Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA). Brain Res 589:349-352.
21. Wu D, Otton SV, Inaba T, Kalow W, and Sellers EM (1997) Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol 53:1605-1612.
22. Young R, Dukat M, Malmusi L, and Glennon RA (1999) Stimulus properties of PMMA: effect of optical isomers and conformational restriction. Pharmacol Biochem Behav 64:449-453.