First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo

Biochemical Pharmacology

Volumn 85, Issue 12, 2013, Pages 1848-1855

  Zhou, Kaidi ^a,b   Khokhar, Jibran Y ^a,b,c   Zhao, Bin ^a,b   Tyndale, Rachel F ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^c DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

Analgesia; Codeine; Cytochrome P450; Drug metabolism; Neuropharmacology; Pharmacokinetics

Indexed keywords

CODEINE; CYTOCHROME P450 2D; MORPHINE; PROPAFENONE; PROPRANOLOL;

ANALGESIA; ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN; BRAIN MEMBRANE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG METABOLISM; EX VIVO STUDY; MALE; METABOLIC ACTIVATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; RAT; TAIL FLICK TEST;

ANALGESIA; ANALGESICS, OPIOID; ANIMALS; BRAIN; CYTOCHROME P-450 CYP2D6; ENZYME INHIBITORS; INJECTIONS, INTRAVENTRICULAR; MALE; PAIN MEASUREMENT; RATS; RATS, WISTAR;

EID: 84878836181     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2013.04.014     Document Type: Article

References (53)

1. S. Miksys, and R.F. Tyndale Brain drug-metabolizing cytochrome P450 enzymes are active in vivo, demonstrated by mechanism-based enzyme inhibition Neuropsychopharmacology 34 2009 634 640
2. S. Miksys, E. Hoffmann, and R.F. Tyndale Regional and cellular induction of nicotine-metabolizing CYP2B1 in rat brain by chronic nicotine treatment Biochem Pharmacol 59 2000 1501 1511 (Pubitemid 30229882)
3. R. Michels, and P.M. Marzuk Progress in psychiatry. 1 N Engl J Med 329 1993 552 560
4. U.M. Zanger, S. Raimundo, and M. Eichelbaum Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry Naunyn-Schmiedeberg's Arch Pharmacol 369 2004 23 37 (Pubitemid 38161221)
5. A. Gaedigk, S.D. Simon, R.E. Pearce, L.D. Bradford, M.J. Kennedy, and J.S. Leeder The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype Clin Pharmacol Ther 83 2008 234 242
6. S. Miksys, and R.F. Tyndale The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics Drug Metab Rev 36 2004 313 333 (Pubitemid 38802491)
7. A. Mann, S. Miksys, A. Lee, D.C. Mash, and R.F. Tyndale Induction of the drug metabolizing enzyme CYP2D in monkey brain by chronic nicotine treatment Neuropharmacology 55 2008 1147 1155
8. S. Miksys, Y. Rao, E. Hoffmann, D.C. Mash, and R.F. Tyndale Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics J Neurochem 82 2002 1376 1387
9. J. Yue, S. Miksys, E. Hoffmann, and R.F. Tyndale Chronic nicotine treatment induces rat CYP2D in the brain but not in the liver: an investigation of induction and time course J Psychiatry Neurosci 33 2008 54 63 (Pubitemid 351252497)
10. M. Warner, and J.A. Gustafsson Effect of ethanol on cytochrome P450 in the rat brain Proc Natl Acad Sci U S A 91 1994 1019 1023 (Pubitemid 24048500)
11. A. Mann, S.L. Miksys, A. Gaedigk, S.J. Kish, D.C. Mash, and R.F. Tyndale The neuroprotective enzyme CYP2D6 increases in the brain with age and is lower in Parkinson's disease patients Neurobiol Aging 33 2012 2160 2171
12. A. Parkinson, D.R. Mudra, C. Johnson, A. Dwyer, and K.M. Carroll The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes Toxicol Appl Pharmacol 199 2004 193 209 (Pubitemid 39208721)
13. T.K. Adler, J.M. Fujimoto, E.L. Way, and E.M. Baker The metabolic fate of codeine in man J Pharmacol Exp Ther 114 1955 251 262
14. C.B. Pert, and S.H. Snyder Properties of opiate-receptor binding in rat brain Proc Natl Acad Sci U S A 70 1973 2243 2247
15. Z.R. Chen, A.A. Somogyi, G. Reynolds, and F. Bochner Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers Br J Clin Pharmacol 31 1991 381 390
16. S.H. Sindrup, K. Brosen, P. Bjerring, L. Arendt-Nielsen, U. Larsen, and H.R. Angelo Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine Clin Pharmacol Ther 48 1990 686 693
17. S.H. Sindrup, L. Arendt-Nielsen, K. Brosen, P. Bjerring, H.R. Angelo, and B. Eriksen The effect of quinidine on the analgesic effect of codeine Eur J Clin Pharmacol 42 1992 587 591
18. M.R. Bouw, M. Gardmark, and M. Hammarlund-Udenaes Pharmacokinetic- pharmacodynamic modelling of morphine transport across the blood-brain barrier as a cause of the antinociceptive effect delay in rats - a microdialysis study Pharm Res 17 2000 1220 1227
19. W.H. Oldendorf, S. Hyman, L. Braun, and S.Z. Oldendorf Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection Science 178 1972 984 986
20. Z.R. Chen, R.J. Irvine, F. Bochner, and A.A. Somogyi Morphine formation from codeine in rat brain: a possible mechanism of codeine-induced analgesia Life Sci 46 1990 1067 1074 (Pubitemid 20148780)
21. S. Miksys, Y. Rao, E.M. Sellers, M. Kwan, D. Mendis, and R.F. Tyndale Regional and cellular distribution of CYP2D subfamily members in rat brain Xenobiotica 30 2000 547 564 (Pubitemid 30449566)
22. Y. Masubuchi, S. Narimatsu, S. Hosokawa, and T. Suzuki Role of the CYP2D subfamily in metabolism-dependent covalent binding of propranolol to liver microsomal protein in rats Biochem Pharmacol 48 1994 1891 1898 (Pubitemid 24355017)
23. K. Rowland, W.W. Yeo, S.W. Ellis, I.G. Chadwick, I. Haq, and M.S. Lennard Inhibition of CYP2D6 activity by treatment with propranolol and the role of 4-hydroxy propranolol Br J Clin Pharmacol 38 1994 9 14 (Pubitemid 24222830)
24. S. Narimatsu, T. Arai, Y. Masubuchi, T. Horie, M. Hosokawa, and K. Ueno Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol Biol Pharm Bull 24 2001 988 994 (Pubitemid 32894115)
25. B.Q. Xu, T.A. Aasmundstad, A. Bjorneboe, A.S. Christophersen, and J. Morland Ethylmorphine O-deethylation in isolated rat hepatocytes. Involvement of codeine O-demethylation enzyme systems Biochem Pharmacol 49 1995 453 460
26. J. Cleary, G. Mikus, A. Somogyi, and F. Bochner The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model J Pharmacol Exp Ther 271 1994 1528 1534 (Pubitemid 24382667)
27. J.W. Lewis, J.E. Sherman, and J.C. Liebeskind Opioid and non-opioid stress analgesia: assessment of tolerance and cross-tolerance with morphine J Neurosci 1 1981 358 363 (Pubitemid 11053808)
28. G. Paxinos, and C. Watson The rat brain in stereotaxic coordinates 2nd ed. 1986 Academic Press San Diego
29. K. Kudo, T. Ishida, N. Nishida, N. Yoshioka, H. Inoue, and A. Tsuji Simple and sensitive determination of free and total morphine in human liver and kidney using gas chromatography-mass spectrometry J Chromatogr B: Anal Technol Biomed Life Sci 830 2006 359 363 (Pubitemid 43075474)
30. R.F. Tyndale, Y. Li, N.Y. Li, E. Messina, S. Miksys, and E.M. Sellers Characterization of cytochrome P-450 2D1 activity in rat brain: high-affinity kinetics for dextromethorphan Drug Metab Dispos 27 1999 924 930 (Pubitemid 29347593)
31. J.F. Ghersi-Egea, R. Perrin, B. Leininger-Muller, M.C. Grassiot, C. Jeandel, and J. Floquet Subcellular localization of cytochrome P450, and activities of several enzymes responsible for drug metabolism in the human brain Biochem Pharmacol 45 1993 647 658 (Pubitemid 23064571)
32. S.V. Bhagwat, M.R. Boyd, and V. Ravindranath Brain mitochondrial cytochromes P450: xenobiotic metabolism, presence of multiple forms and their selective inducibility Arch Biochem Biophys 320 1995 73 83
33. E.C. Siu, D.B. Wildenauer, and R.F. Tyndale Nicotine self-administration in mice is associated with rates of nicotine inactivation by CYP2A5 Psychopharmacology (Berl) 184 2006 401 408 (Pubitemid 43255856)
34. G. Mikus, A.A. Somogyi, F. Bochner, and M. Eichelbaum Codeine O-demethylation: rat strain differences and the effects of inhibitors Biochem Pharmacol 41 1991 757 762
35. B.Q. Xu, T.A. Aasmundstad, A.S. Christophersen, J. Morland, and A. Bjorneboe Evidence for CYP2D1-mediated primary and secondary O-dealkylation of ethylmorphine and codeine in rat liver microsomes Biochem Pharmacol 53 1997 603 609 (Pubitemid 27149555)
36. M. Freiermuth, and J.C. Plasse Determination of morphine and codeine in plasma by HPLC following solid phase extraction J Pharm Biomed Anal 15 1997 759 764 (Pubitemid 27171129)
37. H. He, S.D. Shay, Y. Caraco, M. Wood, and A.J. Wood Simultaneous determination of codeine and its seven metabolites in plasma and urine by high-performance liquid chromatography with ultraviolet and electrochemical detection J Chromatogr B: Biomed Sci Appl 708 1998 185 193 (Pubitemid 28239903)
38. N.L. Kerry, A.A. Somogyi, G. Mikus, and F. Bochner Primary and secondary oxidative metabolism of dextromethorphan. In vitro studies with female Sprague-Dawley and Dark Agouti rat liver microsomes Biochem Pharmacol 45 1993 833 839 (Pubitemid 23071432)
39. U. Bickel, O.P. Schumacher, Y.S. Kang, and K. Voigt Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood-brain barrier in the rat J Pharmacol Exp Ther 278 1996 107 113 (Pubitemid 27167085)
40. Y. Gasche, Y. Daali, M. Fathi, A. Chiappe, S. Cottini, and P. Dayer Codeine intoxication associated with ultrarapid CYP2D6 metabolism N Engl J Med 351 2004 2827 2831 (Pubitemid 40051906)
41. R.F. Tyndale, K.P. Droll, and E.M. Sellers Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence Pharmacogenetics 7 1997 375 379 (Pubitemid 27427547)
42. K. Kathiramalainathan, H.L. Kaplan, M.K. Romach, U.E. Busto, N.Y. Li, and J. Sawe Inhibition of cytochrome P450 2D6 modifies codeine abuse liability J Clin Psychopharmacol 20 2000 435 444 (Pubitemid 30463760)
43. M.K. Romach, S.V. Otton, G. Somer, R.F. Tyndale, and E.M. Sellers Cytochrome P450 2D6 and treatment of codeine dependence J Clin Psychopharmacol 20 2000 43 45 (Pubitemid 30056352)
44. J.C. Nelson, C.M. Mazure, and P.I. Jatlow Desipramine treatment of major depression in patients over 75 years of age J Clin Psychopharmacol 15 1995 99 105
45. M. Ingelman-Sundberg Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity Pharmacogenomics J 5 2005 6 13 (Pubitemid 40220611)
46. H.Y. Lane, W.C. Chiu, J.C.Y. Chou, S.T. Wu, M.H. Su, and W.H. Chang Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels J Clin Psychiatry 61 2000 209 214 (Pubitemid 30214518)
47. M. Riedel, M.J. Schwarz, M. Strassnig, I. Spellmann, A. Muller-Arends, and K. Weber Risperidone plasma levels, clinical response and side-effects Eur Arch Psychiatry Clin Neurosci 255 2005 261 268 (Pubitemid 41187035)
48. B.E. Jabs, A.J. Bartsch, and B. Pfuhlmann Susceptibility to neuroleptic-induced parkinsonism - age and increased substantia nigra echogenicity as putative risk factors Eur Psychiatry 18 2003 177 181 (Pubitemid 36745203)
49. C. Funck-Brentano, P.Y. Boelle, C. Verstuyft, C. Bornert, L. Becquemont, and J.M. Poirier Measurement of CYP2D6 and CYP3A4 activity in vivo with dextromethorphan: sources of variability and predictors of adverse effects in 419 healthy subjects Eur J Clin Pharmacol 61 2005 821 829 (Pubitemid 41720270)
50. R.R. Griffiths, and B. Wolf Relative abuse liability of different benzodiazepines in drug abusers J Clin Psychopharmacol 10 1990 237 243 (Pubitemid 20319176)
51. M. Farre, and J. Cami Pharmacokinetic considerations in abuse liability evaluation Br J Addict 86 1991 1601 1606
52. J.Y. Khokhar, and R.F. Tyndale Drug metabolism within the brain changes drug response: selective manipulation of brain CYP2B alters propofol effects Neuropsychopharmacology 36 2011 692 700
53. J.Y. Khokhar, and R.F. Tyndale Rat brain CYP2B-enzymatic activation of chlorpyrifos to the oxon mediates cholinergic neurotoxicity Toxicol Sci 126 2012 325 335