In silico prediction of drug binding to CYP2D6: identification of a new metabolite of metoclopramide

Drug Metabolism and Disposition

Volumn 34, Issue 8, 2006, Pages 1386-1392

  Yu, Jinglei ^a   Paine, Mark J I ^a   Maréchal, Jean Didier ^b   Kemp, Carol A ^c   Ward, Clive J ^a   Brown, Simon ^a   Sutcliffe, Michael J ^b   Roberts, Gordon C K ^c   Rankin, Elaine M ^a   Wolf, C Roland ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMITRIPTYLINE; ANTIDEPRESSANT AGENT; ANTIDIARRHEAL AGENT; ANTIEMETIC AGENT; ANTIESTROGEN; ANTIULCER AGENT; ANXIOLYTIC AGENT; ATENOLOL; CIMETIDINE; CITALOPRAM; CYTOCHROME P450 2D6; CYTOTOXIC AGENT; DEXAMETHASONE; DILTIAZEM; DOCETAXEL; DOMPERIDONE; FLUOXETINE; HYPOCHOLESTEROLEMIC AGENT; LANSOPRAZOLE; LOPERAMIDE; LORAZEPAM; METOCLOPRAMIDE; OMEPRAZOLE; ONDANSETRON; OXAZEPAM; PREDNISOLONE; RANITIDINE; SIMVASTATIN; TAMOXIFEN;

ANIMAL CELL; ARTICLE; CANCER CHEMOTHERAPY; COMPUTER MODEL; CONTROLLED STUDY; DRUG BINDING; DRUG METABOLISM; ENZYME INHIBITION; EXTRAPYRAMIDAL SYNDROME; GENOTYPE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; IC 50; IN VITRO STUDY; LIVER MICROSOME METABOLISM; MASS SPECTROMETRY; METABOLITE; MOLECULAR MODEL; NAUSEA; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; VOMITING;

ANTIEMETICS; COMPUTER SIMULATION; CYTOCHROME P-450 CYP2D6; DRUG INTERACTIONS; ESCHERICHIA COLI; GENE EXPRESSION; HUMANS; METOCLOPRAMIDE; MICROSOMES, LIVER; MODELS, MOLECULAR; NADPH-FERRIHEMOPROTEIN REDUCTASE; PHARMACEUTICAL PREPARATIONS;

EID: 33746042623     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.106.009852     Document Type: Article

References (47)

1. Baguley WA, Hay WT, Mackie KP, Cheney FW, and Cullen BF (1997) Cardiac dysrhythmias associated with the intravenous administration of ondansetron and metoclopramide. Anesth Analg 84:1380-1381.
2. Bateman DN, Kahn C, and Davies DS (1980) The pharmacokinetics of metoclopramide in man with observations in the dog. Br J Clin Pharmacol 9:371-377.
3. Crewe HK, Notley LM, Wunsch RM, Lennard MS, and Gillam EM (2002) Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4′-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos 30:869-874.
4. Cupp-Vickery J, Anderson R, and Hatziris Z (2000) Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity. Proc Natl Acad Sci USA 97:3050-3055.
5. Dehal SS and Kupfer D (1997) CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res 57:3402-3406.
6. Desta Z, Ward BA, Soukhova NV, and Flockhart DA (2004) Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310:1062-1075.
7. Desta Z, Wu GM, Morocho AM, and Flockhart DA (2002) The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6. Drug Metab Dispos 30:336-343.
8. Ekins S, Berbaum J, and Harrison RK (2003) Generation and validation of rapid computational filters for cyp2d6 and cyp3a4. Drug Metab Dispos 31:1077-1080.
9. Eldridge MD, Murray CW, Auton TR, Paolini GV, and Mee RP (1997) Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J Comput Aided Mol Des 11:425-445.
10. Flanagan JU, Marechal JD, Ward R, Kemp CA, McLaughlin LA, Sutcliffe MJ, Roberts GC, Paine MJ, and Wolf CR (2004) Phe120 contributes to the regiospecificity of cytochrome P450 2D6: mutation leads to the formation of a novel dextromethorphan metabolite. Biochem J 380:353-360.
11. Grant SC, Close JR, and Bray CL (1994) Methaemoglobinaemia produced by metoclopramide in an adult. Eur J Clin Pharmacol 47:89.
12. Harrington RA, Hamilton CW, Brogden RN, Linkewich JA, Romankiewicz JA, and Heel RC (1983) Metoclopramide. An updated review of its pharmacological properties and clinical use. Drugs 25:451-494.
13. Hasemann CA, Ravichandran KG, Peterson JA, and Deisenhofer J (1994) Crystal structure and refinement of cytochrome P450terp at 2.3 A resolution. J Mol Biol 236:1169-1185.
14. Jimenez-Jimenez FJ, Garcia-Ruiz PJ, and Molina JA (1997) Drug-induced movement disorders. Drug Saf 16:180-204.
15. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, et al. (2005) CYP2D6 genotype, antidepressant use and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30-39.
16. Jones G, Willett P, Glen RC, Leach AR, and Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267:727-748.
17. Keizers PH, de Graaf C, de Kanter FJ, Oostenbrink C, Feenstra KA, Commandeur JN, and Vermeulen NP (2005) Metabolic regio- and stereoselectivity of cytochrome P450 2D6 towards 3,4-methylenedioxy-N-alkylamphetamines: in silico predictions and experimental validation. J Med Chem 48:6117-6127.
18. Keizers PH, Lussenburg BM, de Graaf C, Mentink LM, Vermeulen NP, and Commandeur JN (2004) Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and regiospecificity: crucial role in 7-methoxy-4- (aminomethyl)-coumarin metabolism. Biochem Pharmacol 68:2263-2271.
19. Kellenberger E, Rodrigo J, Muller P, and Rognan D (2004) Comparative evaluation of eight docking tools for docking and virtual screening accuracy. Proteins 57:225-242.
20. Kemp CA, Flanagan JU, van Eldik AJ, Marechal JD, Wolf CR, Roberts GC, Paine MJ, and Sutcliffe MJ (2004) Validation of model of cytochrome P450 2D6: an in silico tool for predicting metabolism and inhibition. J Med Chem 47:5340-5346.
21. Kim KA, Chung J, Jung DH, and Park JY (2004) Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol 60:575-581.
22. Kirton SB, Kemp CA, Tomkinson NP, St-Gallay S, and Sutcliffe MJ (2002) Impact of incorporating the 2C5 crystal structure into comparative models of cytochrome P450 2D6. Proteins 49:216-231.
23. Kirton SB, Murray CW, Verdonk ML, and Taylor RD (2005) Prediction of binding modes for ligands in the cytochromes P450 and other heme-containing proteins. Proteins 58:836-844.
24. Kontoyianni M, McClellan LM, and Sokol GS (2004) Evaluation of docking performance: comparative data on docking algorithms. J Med Chem 47:558-565.
25. Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, et al. (2001) Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 27:383-391.
26. Langford JS and Sheikh S (1999) An adolescent case of sulfhemoglobinemia associated with high-dose metoclopramide and N-acetylcysteine. Ann Emerg Med 34:538-541.
27. Malkoff MD, Ponzillo JJ, Myles GL, Gomez CR, and Cruz-Flores S (1995) Sinus arrest after administration of intravenous metoclopramide. Ann Pharmacother 29:381-383.
28. Marechal JD, Yu J, Brown S, Kapelioukh I, Rankin EM, Wolf CR, Roberts GC, Paine MJ, and Sutcliffe MJ (2006) In silico and in vitro screening for inhibition of cytochrome P450 CYP3A4 by comedications commonly used by patients with cancer. Drug Metab Dispos 34:534-538.
29. Margolis JM, O'Donnell JP, Mankowski DC, Ekins S, and Obach RS (2000) (R)-, (S)- and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab Dispos 28:1187-1191.
30. Maurich V, De Amici M, and De Micheli C (1994) Synthesis of a metabolite of metoclopramide and its detection in human urine. Farmaco 49:805-808.
31. McLaughlin LA, Paine MJ, Kemp CA, Marechal JD, Flanagan JU, Ward CJ, Sutcliffe MJ, Roberts GC, and Wolf CR (2005) Why is quinidine an inhibitor of cytochrome P450 2D6? The role of key active-site residues in quinidine binding. J Biol Chem 280:38617-38624.
32. Molden E, Asberg A, and Christensen H (2000) CYP2D6 is involved in O-demethylation of diltiazem. An in vitro study with transfected human liver cells. Eur J Clin Pharmacol 56:575-579.
33. Olesen OV and Linnet K (1997) Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology 55:235-243.
34. Paine MJ, McLaughlin LA, Flanagan JU, Kemp CA, Sutcliffe MJ, Roberts GC, and Wolf CR (2003) Residues glutamate 216 and aspartate 301 are key determinants of substrate specificity and product regioselectivity in cytochrome P450 2D6. J Biol Chem 278:4021-4027.
35. Poulos TL, Finzel BC, and Howard AJ (1986) Crystal structure of substrate-free Pseudomonas putida cytochrome P-450. Biochemistry 25:5314-5322.
36. Radomski JL (1979) The primary aromatic amines: their biological properties and structure-activity relationships. Annu Rev Pharmacol Toxicol 19:129-157.
37. Ravichandran KG, Boddupalli SS, Hasermann CA, Peterson JA, and Deisenhofer J (1993) Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science (Wash DC) 261:731-736.
38. Rochat B, Amey M, Gillet M, Meyer UA, and Baumann P (1997) Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics 7:1-10.
39. Rowland P, Blaney FE, Smyth MG, Jones JJ, Leydon VR, Oxbrow AK, Lewis CJ, Tennant MG, Modi S, Eggleston DS, et al. (2006) Crystal structure of human cytochrome P450 2D6. J Biol Chem 281:7614-7622.
40. Sali A and Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234:779-815.
41. Teng L, Bruce RB, and Dunning LK (1977) Metoclopramide metabolism and determination by high-pressure liquid chromatography. J Pharm Sci 66:1615-1618.
42. van de Waterbeemd H and Gifford E (2003) ADMET in silico modelling: towards prediction paradise? Nat Rev Drug Discov 2:192-204.
43. Venhorst J, ter Laak AM, Commandeur JN, Funae Y, Hiroi T, and Vermeulen NP (2003) Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities. J Med Chem 46:74-86.
44. Verdonk ML, Cole JC, Hartshorn MJ, Murray CW, and Taylor RD (2003) Improved protein-ligand docking using GOLD. Proteins 52:609-623.
45. Ward BA, Morocho A, Kandil A, Galinsky RE, Flockhart DA, and Desta Z (2004) Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. Br J Clin Pharmacol 58:277-287.
46. Williams PA, Cosme J, Sridhar V, Johnson EF, and McRee DE (2000) Microsomal cytochrome P450 2C5: comparison to microbial P450s and unique features. J Inorg Biochem 81:183-190.
47. Wolf CR, Smith G, and Smith RL (2000) Science, medicine, and the future: pharmacogenetics. BMJ 320:987-990.