N-Demethylation of levo-α-acetylmethadol by human placental aromatase

Biochemical Pharmacology

Volumn 67, Issue 5, 2004, Pages 885-892

  Deshmukh, Sujal V ^a   Nanovskaya, Tatiana N ^a   Hankins, Gary D V ^a   Ahmed, Mahmoud S ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

Author keywords

Aromatase; Human placenta; LAAM; Metabolism; Opiate addict

Indexed keywords

AROMATASE; CYTOCHROME P450; LEVACETYLMETHADOL; NORACYMETHADOL; PLACENTA ENZYME; UNCLASSIFIED DRUG;

ARTICLE; BIOTRANSFORMATION; BLOOD PLACENTA BARRIER; CATALYSIS; CELL ACTIVITY; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOSOLIC FRACTION; DEMETHYLATION; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN TISSUE; MICROSOME; PLACENTA CIRCULATION; PLACENTA MICROSOME; PRIORITY JOURNAL; PROTEIN EXPRESSION; ULTRAVIOLET SPECTROSCOPY;

EID: 1042263306     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2003.10.007     Document Type: Article

References (29)

1. Eissenberg T., Stitzer M.L., Bigelow G.E., Buchhalter A.R., Walsh S.L. Relative potency of levoalpha-acetylmethadol and methadone in humans under acute dosing conditions. J. Pharmacol. Exp. Ther. 289:1999;936-945.
2. Clark N., Lintzeris N., Gijsbers A., Whelan G., Dunlop A., Ritter A., Ling W. LAAM maintenance vs. methadone maintenance for heroin dependence. Cochrane Database Syst. Rev. 2:2000;CD002210.
3. O'Connor P.G., Fiellin D.A. Pharmacologic treatment of heroin-dependent patients. Ann. Intern. Med. 133:2000;40-54.
4. Billings R.E., Booher R., Smits S., Pohland A., McMahon R.E. Metabolism of acetylmethadol. A sensitive assay for noracetylmethadol and the identification of a new active metabolite. J. Med. Chem. 16:1973;305-306.
5. Kaiko R.F., Inturrisi C.E. Disposition of acetylmethadol in relation to pharmacologic action. Clin. Pharmacol. Ther. 18:1975;96-103.
6. Vaupel D.B., Jasinski D.R. l-Alpha-acetylmethadol, l-alpha-acetyl-N- normethadol and l-alphaacetyl-N,N-dinormethadol: comparisons with morphine and methadone in suppression of the opioid withdrawal syndrome in the dog. J. Pharmacol. Exp. Ther. 283:1997;833-842.
7. Walsh S.L., Johnson R.E., Cone E.J., Bigelow G.E. Intravenous and oral L-α-acetylmethadol: pharmacodynamics and pharmacokinetics in humans. J. Pharmacol. Exp. Ther. 285:1998;71-82.
8. Walczak S.A., Makman M.H., Gardner E.L. Acetylmethadol metabolites influence opiate receptors and adenylate cyclase in amygdala. Eur. J. Pharmacol. 72:1981;343-349.
9. Horng J.S., Smits S.E., Wong D.T. The binding of the optical isomers of methadone, alphamethadol, alpha-acetylmethadol and their N-demethylated derivatives to the opiate receptors of rat brain. Res. Commun. Chem. Pathol. Pharmacol. 14:1976;621-629.
10. Smits S.E. The analgesic activity of alpha-1-acetylmethadol and two of its metabolites in mice. Res. Commun. Chem. Pathol. Pharmacol. 8:1974;575-578.
11. Nanovskaya T.N., Deshmukh S.V., Miles R., Burmaster S., Ahmed M.S. Transfer of L-alphaacetylmethadol (LAAM) and L-alpha-acetyl-N-normethadol (norLAAM) by the perfused human placental lobule. J. Pharmacol. Exp. Ther. 306:2003;205-212.
12. Van Petten G.R., Hirsch G.H., Cherrington A.D. Drug-metabolizing activity of the human placenta. Can. J. Biochem. 46:1968;1057-1061.
13. Blanck A., Rane A., Toftgard R., Gustafsson J.A. Biotransformation of benzo[a]pyrene and 7-ethoxyresorufin and heme-staining proteins in microsomes from human fetal liver and placenta. Biochem. Pharmacol. 32:1983;1547-1552.
14. Pasanen M., Raunio H., Pelkonen O. Freezing affects the activity and subcellular distribution profile of human placental xenobiotic and steroid-metabolizing enzymes. Placenta. 6:1985;527-535.
15. Pasanen M., Pelkonen O. Xenobiotic and steroid-metabolizing monooxygenases catalysed by cytochrome P450 and glutathione S-transferase conjugations in the human placenta and their relationships to maternal cigarette smoking. Placenta. 11:1990;75-85.
16. Roe D.A., Little B.B., Bawdon R.E., Gilstrap L.C. III Metabolism of cocaine by human placentas: implications for fetal exposure. Am. J. Obstet. Gynecol. 163:1990;715-718.
17. Juchau M.R. Drug biotransformation in the placenta. Pharmacol. Ther. 8:1980;501-524.
18. Hakkola J., Pelkonen O., Pasanen M., Raunio H. Xenobiotic-metabolizing cytochrome P450 enzymes in the human feto-placental unit: role in intrauterine toxicity. Crit. Rev. Toxicol. 28:1998;35-72.
19. Audus K.L. Controlling drug delivery across the placenta. Eur. J. Pharm. Sci. 8:1999;161-165.
20. Moody D.E., Alburges M.E., Parker R.J., Collins J.M., Strong J.M. The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone. Drug Metab. Dispos. 25:1997;1347-1353.
21. Oda Y., Kharasch E.D. 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. 297:2001;410-422.
22. Oda Y., Kharasch E.D. Metabolism of methadone and levo-alpha- acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation. J. Pharmacol. Exp. Ther. 298:2001;1021-1032.
23. Neff J.A., Moody D.E. Differential N-demethylation of l-alpha-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18, and 3A4. Biochem. Biophys. Res. Commun. 284:2001;751-756.
24. Newton D.J., Wang R.W., Lu A.Y. Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab. Dispos. 23:1995;154-158.
25. Bourrie M., Meunier V., Berger Y., Fabre G. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J. Pharmacol. Exp. Ther. 277:1996;321-332.
26. Stresser D.M., Turner S.D., McNamara J., Stocker P., Miller V.P., Crepsi C.L., Patten C.J. A highthroughput screen to identify inhibitors of aromatase (CYP19). Anal. Biochem. 284:2000;427-430.
27. Pasanen M. The expression and regulation of drug metabolism in human placenta. Adv. Drug Deliv. Rev. 38:1999;81-97.
28. Pasanen M. Human placental aromatase activity: use of a C18 reversed-phase cartridge for separation of tritiated water or steroid metabolites in placentas from both smoking and nonsmoking mothers in vitro. Biol. Res. Pregnancy Perinatol. 6:1985;94-99.
29. Deshmukh S.V., Nanovskaya T.N., Ahmed M.S. Aromatase is the major enzyme metabolizing buprenorphine in human placenta. J. Pharmacol. Exp. Ther. 306:2003;1099-1105.