Drug metabolism within the brain changes drug response: Selective manipulation of brain CYP2B alters propofol effects

Neuropsychopharmacology

Volumn 36, Issue 3, 2011, Pages 692-700

  Khokhar, Jibran Y ^a   Tyndale, Rachel F ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

anesthesia; brain; cytochrome P450; metabolism; propofol; sleep

Indexed keywords

C8 XANTHATE; CYTOCHROME P450; CYTOCHROME P450 2A; CYTOCHROME P450 2B; CYTOCHROME P450 2D; CYTOCHROME P450 2E; CYTOCHROME P450 3A; LIVER ENZYME; METHOXSALEN; NICOTINE; PROPOFOL; UNCLASSIFIED DRUG; XANTHIC ACID DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN METABOLISM; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG METABOLISM; DRUG RESPONSE; DRUG SELECTIVITY; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME INHIBITION; LIVER; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SLEEP TIME;

ANALYSIS OF VARIANCE; ANESTHETICS, INTRAVENOUS; ANIMALS; BRAIN; CHLORISONDAMINE; CYTOCHROME P-450 CYP2B1; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; ENZYME INHIBITORS; INJECTIONS, INTRAVENTRICULAR; MALE; METABOLIC DETOXICATION, DRUG; METHOXSALEN; NICOTINE; NICOTINIC AGONISTS; NICOTINIC ANTAGONISTS; PROPOFOL; RATS; RATS, WISTAR; SLEEP; TIME FACTORS; TRITIUM;

EID: 78651385372     PISSN: 0893133X     EISSN: None     Source Type: Journal    
DOI: 10.1038/npp.2010.202     Document Type: Article

References (48)

1. Albores A, Ortega-Mantilla G, Sierra-Santoyo A, Cebrian ME, Munoz-Sanchez JL, Calderon-Salinas JV et al (2001). Cyto-chrome P450 2B (CYP2B)-mediated activation of methyl-parathion in rat brain extracts. Toxicol Lett 124: 1-10.
2. Altomare C, Trapani G, Latrofa A, Serra M, Sanna E, Biggio G et al (2003). Highly water-soluble derivatives of the anesthetic agent propofol: in vitro and in vivo evaluation of cyclic amino acid esters. Eur J Pharm Sci 20: 17-26.
3. Bhargava VK, Saha L (2001). Cholinergic mechanism in imipra-mine and morphine antinoception. Boll Chim Farm 140: 201-204. (Pubitemid 32953872)
4. Bijl MJ, Luijendijk HJ, van den Berg JF, Visser LE, van Schaik RH, Hofman A et al (2009). Association between the CYP2D6*4 polymorphism and depression or anxiety in the elderly. Pharmacogenomics 10: 541-547.
5. Bromek E, Haduch A, Daniel WA (2010). The ability of cytochrome P450 2D isoforms to synthesize dopamine in the brain: an in vitro study. Eur J Pharmacol 626: 171-178.
6. Cavazzuti M, Porro CA, Barbieri A, Galetti A (1991). Brain and spinal cord metabolic activity during propofol anaesthesia. Br J Anaesth 66: 490-495.
7. Challet E, Gourmelen S, Pevet P, Oberling P, Pain L (2007). Reciprocal relationships between general (propofol) anesthesia and circadian time in rats. Neuropsychopharmacology 32: 728-735.
8. Chimbira W, Sweeney BP (2000). The effect of smoking on postoperative nausea and vomiting. Anaesthesia 55: 540-544.
9. Clarke PB, Chaudieu I, el-Bizri H, Boksa P, Quik M, Esplin BA et al (1994). The pharmacology of the nicotinic antagonist, chlor-isondamine, investigated in rat brain and autonomic ganglion. Br J Pharmacol 111: 397-405.
10. Court MH, Duan SX, Hesse LM, Venkatakrishnan K, Greenblatt DJ (2001). Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver micro-somes. Anesthesiology 94: 110-119.
11. Dam M, Ori C, Pizzolato G, Ricchieri GL, Pellegrini A, Giron GP et al (1990). The effects of propofol anesthesia on local cerebral glucose utilization in the rat. Anesthesiology 73: 499-505.
12. Ekins S, Iyer M, Krasowski MD, Kharasch ED (2008). Molecular characterization of CYP2B6 substrates. Curr Drug Metab 9: 363-373.
13. Fassoulaki A, Farinotti R, Mantz J, Desmonts JM (1994). Does tolerance develop to the anaesthetic effects of propofol in rats? Br J Anaesth 72: 127-128.
14. Fassoulaki A, Farinotti R, Servin F, Desmonts JM (1993). Chronic alcoholism increases the induction dose of propofol in humans. Anesth Analg 77: 553-556.
15. Favetta P, Degoute CS, Perdrix JP, Dufresne C, Boulieu R, Guitton J (2002). Propofol metabolites in man following propofol induction and maintenance. Br J Anaesth 88: 653-658.
16. Fradette C, Yamaguchi N, Du Souich P (2004). 5-Hydroxytrypta-mine is biotransformed by CYP2C9, 2C19 and 2B6 to hydro-xylamine, which is converted into nitric oxide. Br J Pharmacol 141: 407-414.
17. Gervasini G, Carrillo JA, Benitez J (2004). Potential role of cerebral cytochrome P450 in clinical pharmacokinetics: modulation by endogenous compounds. Clin Pharmacokinet 43: 693-706.
18. 0 Brien JK, Cunningham AJ, Fitzgerald DF, Shields DC (2007). An investigation of potential genetic determinants of propofol requirements and recovery from anaesthesia. Eur J Anaesthesiol 24: 912-919.
19. Kanto J, Gepts E (1989). Pharmacokinetic implications for the clinical use of propofol. Clin Pharmacokinet 17: 308-326.
20. Khokhar JY, Miksys SL, Tyndale RF (2010). Rat brain CYP2B induction by nicotine is persistent and does not involve nicotinic acetylcholine receptors. Brain Res 1348: 1-9.
21. Kirchheiner J, Seeringer A, Godoy AL, Ohmle B, Maier C, Beschoner P et al (2010). CYP2D6 in the brain: genotype effects on resting brain perfusion. Mol Psychiatry (e-pub ahead of print 6 April 2010; doi:10.138/mp.2010.42).
22. Koenigs LL, Trager WF (1998). Mechanism-based inactivation of cytochrome P450 2B1 by 8-methoxypsoralen and several other furanocoumarins. Biochemistry 37: 13184-13193.
23. Langley MS, Heel RC (1988). Propofol. A review of its pharmacodynamic and pharmacokinetic properties and use as an intravenous anaesthetic. Drugs 35: 334-372.
24. Le Guellec C, Lacarelle B, Villard PH, Point H, Catalin J, Durand A (1995). Glucuronidation of propofol in microsomal fractions from various tissues and species including humans: effect of different drugs. Anesth Analg 81: 855-861.
25. Lewis D (1996). Cytochromes P450. Structure, Function and Mechanism. Taylor & Francis: Bristol. pp 122-123.
26. Liu SH, Wei W, Ding GN, Ke JD, Hong FX, Tian M (2009). Relationship between depth of anesthesia and effect-site concentration of propofol during induction with the target-controlled infusion technique in elderly patients. Chin Med J (Engl) 122: 935-940.
27. Ludbrook GL, Upton RN, Grant C, Gray EC (1996). Brain and blood concentrations of propofol after rapid intravenous injection in sheep, and their relationships to cerebral effects. Anaesth Intens Care 24: 445-452.
28. Lukas G, Brindle SD, Greengard P (1971). The route of absorption of intraperitoneally administered compounds. J Pharmacol Exp Ther 178: 562-564.
29. Lysakowski C, Dumont L, Czarnetzki C, Bertrand D, Tassonyi E, Tramer MR (2006). The effect of cigarette smoking on the hypnotic efficacy of propofol. Anaesthesia 61: 826-831.
30. Mann A, Tyndale RF (2010). Cytochrome P450 2D6 enzyme neuroprotects against 1-methyl-4-phenylpyridinium toxicity in SH-SY5Y neuronal cells. Eur J Neurosci 31: 1185-1193.
31. Meyer RP, Gehlhaus M (2010). A role for CYP in the drug- hormone crosstalk of the brain. Expert Opin Drug Metab Toxicol 6: 675-687.
32. Michels R, Marzuk PM (1993). Progress in psychiatry (1). N Engl J Med 329: 552-560.
33. Miksys S, Lerman C, Shields PG, Mash DC, Tyndale RF (2003). Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain. Neuropharmacology 45: 122-132.
34. Miksys S, Tyndale RF (2004). The unique regulation of brain cytochrome P450 2 (CYP2) family enzymes by drugs and genetics. Drug Metab Rev 36: 313-333.
35. Miksys S, Tyndale RF (2009). Brain drug-metabolizing cyto-chrome P450 enzymes are active in vivo, demonstrated by mechanism-based enzyme inhibition. Neuropsychopharmacology 34: 634-640.
36. Miksys SL, Tyndale RF (2002). Drug-metabolizing cytochrome P450s in the brain. J Psychiatry Neurosci 27: 406-415.
37. Nakayama H, Okuda H, Nakashima T, Imaoka S, Funae Y (1993). Nicotine metabolism by rat hepatic cytochrome P450s. Biochem Pharmacol 45: 2554-2556.
38. Paxinos G, Watson C (1986). The Rat Brain in Stereotaxic Coordinates, 2nd edn. Academic Press: San Diego.
39. Sebel PS, Lowdon JD (1989). Propofol: a new intravenous anesthetic. Anesthesiology 71: 260-277.
40. Seno H, He YL, Tashiro C, Ueyama H, Mashimo T (2002). Simple high-performance liquid chromatographic assay of propofol in human and rat plasma and various rat tissues. J Anesth 16: 87-89.
41. Shyr MH, Tsai TH, Tan PP, Chen CF, Chan SH (1995). Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat. Neurosci Lett 184: 212-215.
42. Siu EC, Tyndale RF (2008). Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice. J Pharmacol Exp Ther 324: 992-999.
43. Strobel HW, Thompson CM, Antonovic L (2001). Cytochromes P450 in brain: function and significance. Curr Drug Metab 2: 199-214.
44. Tassonyi E, Charpantier E, Muller D, Dumont L, Bertrand D (2002). The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia. Brain Res Bull 57: 133-150. (Pubitemid 34155386)
45. Upadhya SC, Chinta SJ, Pai HV, Boyd MR, Ravindranath V (2002). Toxicological consequences of differential regulation of cyto-chrome p450 isoforms in rat brain regions by phenobarbital. Arch Biochem Biophys 399: 56-65.
46. Vallejo YF, Buisson B, Bertrand D, Green WN (2005). Chronic nicotine exposure upregulates nicotinic receptors by a novel mechanism. J Neurosci 25: 5563-5572.
47. Yanev S, Kent UM, Pandova B, Hollenberg PF (1999). Selective mechanism-based inactivation of cytochromes P-450 2B1 and P-450 2B6 by a series of xanthates. Drug Metab Dispos 27: 600-604. (Pubitemid 29214472)
48. Yanev SG, Kent UM, Roberts ES, Ballou DP, Hollenberg PF (2000). Mechanistic studies of cytochrome P450 2B1 inactivation by xanthates. Arch Biochem Biophys 378: 157-166.