Irreversible inhibition of CYP2D6 by (-)-chloroephedrine, a possible impurity in methamphetamine

Drug Metabolism and Disposition

Volumn 30, Issue 12, 2002, Pages 1337-1343

  Rege, B ^a   Carter, K M ^a   Sarkar, M A ^a   Kellogg, G E ^a   Soine, W H ^a,b  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b Box 980540 ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHLOROEPHEDRINE; CYTOCHROME P450 1A2; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DEXTROMETHORPHAN; EPHEDRINE DERIVATIVE; METHAMPHETAMINE; UNCLASSIFIED DRUG; DRUG DERIVATIVE; EPHEDRINE;

ARTICLE; BINDING AFFINITY; BINDING SITE; CIS TRANS ISOMERISM; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; ENZYME ACTIVE SITE; ENZYME INHIBITION; HUMAN; HUMAN CELL; LIVER MICROSOME; MOLECULAR MODEL; PRIORITY JOURNAL; CHEMISTRY; DRUG ANTAGONISM; DRUG CONTAMINATION; ENZYMOLOGY; METABOLISM;

CYTOCHROME P-450 CYP2D6; DRUG CONTAMINATION; EPHEDRINE; HUMANS; METHAMPHETAMINE; MICROSOMES, LIVER;

EID: 0036891985     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.30.12.1337     Document Type: Article

References (38)

1. Allen TS and Kiser WO (1987) Methamphetamine from ephedrine: 1. Chloroephedrines and aziridines. J Forensic Sci 32:953-962.
2. Burke MD and Mayer RT (1974) Ethoxyresorufin: Direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene. Drug Metab Dispos 2:583-588.
3. Cantrell TS, John B, Johnson L, and Allen AC (1988) A study of impurities found in methamphetamine synthesized from ephedrine. Forensic Sci Int 39:39-53.
4. deGroot MJ, Ackland MJ, Horne VA, Alex AA, and Jones BC (1999) Novel approach to predicting P450-mediated drug metabolism: Development of a combined protein and pharmacophore model for CYP2D6. J Med Chem 42:1515-1524.
5. deGroot MJ, Bijloo GJ, Martens BJ, van Acker FAA, and Vermeulen NPE (1997) A refined substrate model for human cytochrome P450 2D6. Chem Res Toxicol 10:41-48.
6. Ellis SW, Hayhurst GP, Smith G, Lightfoot T, Wong MMS, Simula AP, Ackland MJ, Sternberg MJE, Lennard MS, Tucker GT, and Wolf CR (1995) Evidence that aspartic acid 301 is a critical substrate-contact residue in the active site of cytochrome P450 2D6. J Biol Chem 270:29055-29058.
7. Ellis SW, Rowland K, Ackland MJ, Rekka E, Simula AP, Lennard MS, Wolk CR, and Tucker GT (1996) Influence of amino acid residue 374 of cytochrome P450 2D6 (CYP2D6) on the regio- and enantioselectivity metabolism of metoprolol. Biochem J 316:647-654.
8. th Ed, chapter 15, pp 109-140, Loompanics Unlimited, Port Townsend, WA.
9. Hata Y and Watanabe M (1994) Metabolism of aziridines and the mechanism of their cytotoxicity. Drug Metab Rev 26:575-604.
10. Hata Y, Watanabe M, Matsubara T, and Touchi A (1976) Fragmentation reaction of ylide. 5. A new metabolic reaction of aziridine derivatives. J Am Chem Soc 98:6033-6036.
11. Henkel JG, Portoghese PS, Miller JW, and Lewis P (1976) Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine. J Med Chem 19:6-10.
12. Islam SA, Wolf CR, Lennard MS, and Sternberg MJE (1991) A three-dimensional molecular template for substrates of human cytochrome P450 involved in debrisoquine 4-hydroxylation. Carcinogenesis 12:2211-2219.
13. o/w more than the sum of its parts? Eur J Med Chem 35:651-661.
14. Ketema H, Davis WM, Walker LA, and Borne RF (1990) Pharmacologic and toxicologic effects of di(β-phenylisopropyl)amine (DPIA) in rats and mice. Gen Pharmac 21:783-790.
15. Kitz R and Wilson IB (1962) Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. J Biol Chem 237:3245-3249.
16. Koymans LMH, Vermeulen NPE, Baarslag A, and Donne-Op den Kelder GMA (1993) A preliminary 3D model for cytochrome P-450 2D6 constructed by homology model building. J Comput-Aided Mol Design 7:281-289.
17. Langston JW, Ballard P, Tetrud JW, and Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science (Wash DC) 219:979-980.
18. Lekskulchai V, Carter K, Poklis A, and Soine WH (2000) GC/MS analysis of methamphetamine impurities: Reactivity of (+)- or (-)-chloroephedrine and cis- or trans-1, 2-dimethyl-3-phenyl aziridine. J Anal Tox 24:602-605.
19. Lewis DFV, Eddershaw PJ, Goldfard PS, and Tarbit MH (1997) Molecular modeling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP102: Structural studies on specific CYP2D6 substrate metabolism. Xenobiotica 27:319-340.
20. Louw A, Swart P, de Kock SS, and van der Merwe KJ (1997) Mechanism for the stabilization in vivo of the aziridine precursor-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride by serum proteins. Biochem Pharmacol 53:189-197.
21. Modi S, Paine MJ, Sutcliffe MJ, Lian L-Y, Primrose WU, Wolf CR, and Roberts GCK (1996) A model for human cytochrome P450 2D6 based on homology modeling and NMR studies of substrate binding. Biochemistry 35:4540-4540.
22. Moore KA, Lichtman AH, Poklis A, and Borzelleca JF (1995) α-benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: Pharmacological evaluation and interaction with methamphetamine. Drug Alcohol Depend 39:83-89.
23. Moore KA, Mirshahi T, Compton DR, Poklis A, and Woodward JJ (1996) Pharmacological characterization of BNMPA (α-benzyl-N-methylphenethylamine), an impurity of illicit methamphetamine synthesis. Eur J Pharmacol 311:133-139.
24. Noggle FT, Clark CR, Davenport TW, and Coker ST (1985) Synthesis, identification and acute toxicity of α-benzyl-N-methylphenethylamine. Contaminants in clandestine preparation of amphetamine and methamphetamine. J Assoc Off Anal Chem 68:1213-1222.
25. Noggle FT, DeRuiter J, and Clark CR (1986) Liquid chromatographic determination of the enantiomeric composition of methamphetamine prepared from ephedrine and pseudoephedrine. Anal Chem 58:1643-1648.
26. Palamanda JR, Casciano CN, Norton LA, Clement RP, Favreau LV, Lin C-C, and Nomeir AA (2001) Mechanism-based inactivation of CYP2D6 by 5-fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]pyridine. Drug Metab Dispos 29:863-867.
27. Rege B, March C, and Sarkar MA (2002) Development of a rapid and sensitive high-performance liquid chromatographic method to determine CYP2D6 phenotype in human liver microsomes. Biomed Chromatogr 16:31-40.
28. Skinner HF (1990) Methamphetamine synthesis via hydriodic acid/red phosphorous reduction of ephedrine. Forensic Sci Int 48:123-134.
29. Strobl GR, von Kreudener S, Stockigt J, Geungerich FP, and Wolff T (1993) Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: Molecular modeling and inhibition studies. J Med Chem 36:1136-1145.
30. Taguchi T and Kojima M (1959) The formation and chemical properties of diastereomeric 1,2-dimethyl-3-phenylaziridine. Chem Pharm Bull 7:103-107.
31. Tanaka K, Ohmori T, and Inoue T (1992) Analysis of Impurities in Illicit Methamphetamine. Forensic Sci Int 56:157-165.
32. Thomas EA, Hsu HH, Griffin MT, Hunter AL, Luong T, and Ehlert FJ (1992) Conversion of N-(2-chloroethyl)-4-piperidinyl diphenylacetate to an aziridinium ion and its interaction with muscarinic receptors in various tissues. Mol Pharmacol 41:718-726.
33. Tyndale RF, Li Y, Li N-Y, Messina E, Miksys S, and Sellers EM (1999) Characterization of cytochrome P-450 2D1 activity in rat brain: High-affinity kinetics for dextromethorphan. Drug Metab Dispos 27:924-930.
34. U.S. Department of Justice, Drug Enforcement Administration (1998) The NNICC Report 1997: The Supply of Illicit Drugs to the United States. U.S. Government Printing Office, Washington, DC.
35. Varner KJ, Hein ND, Ogden BA, Arsenault JR, Carter KM, and Soine WH (2001) Chloroephedrine: Contaminant of methamphetamine synthesis with cardiovascular activity. Drug Alcohol Depend 64:299-307.
36. Verweij AMA (1989) Impurities in illicit drug preparations: Amphetamine and methamphetamine. Forensic Sci Rev 1:2-11.
37. 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.
38. Yu A and Haining RL (2001) Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: Can dextromethorphan be used as a dual probe for both CYP2D6 and CYP3A activities? Drug Metab Dispos 29:1514-1520.