Identification of phase-I metabolites and chronic toxicity study of the Kv1.3 blocker PAP-1 (5-(4-phenoxybutoxy)psoralen) in the rat

Xenobiotica

Volumn 41, Issue 3, 2011, Pages 198-211

  Hao, B ^a   Chen, Z W ^a   Zhou, X J ^a   Zimin, P I ^b   Miljanich, G P ^c   Wulff, H ^b   Wang, Y X ^a  

^a SHANGHAI JIAO TONG UNIVERSITY   (China)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c Airmid LLC   (United States)

Author keywords

5 (4 phenoxybutoxy)psoralen (PAP 1); CYP isoenzyme; Kv1.3 activity; Kv1.3 blocker; metabolite; O dealkylation

Indexed keywords

5 (4 PHENOXYBUTOXY)PSORALEN; 5 (OXYBUTYRIC ACID)PSORALEN; 5 [4 (3 HYDROXYPHENOXY)BUTOXY]PSORALEN; 5 [4 (4 HYDROXYBUTOXY)]PSORALEN; 5 [4(4 HYDROXYPHENOXY)BUTOXY]PSORALEN; 8 HYDROXYL 5 (4 PHENOXYBUTOXY)PSORALEN; ALPHA NAPHTHOFLAVONE; CYTOCHROME P450; DIETHYLDITHIOCARBAMIC ACID; KETOCONAZOLE; NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) TRANSHYDROGENASE; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL KV1.3; QUINIDINE; SULFAPHENAZOLE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DEALKYLATION; DRUG IDENTIFICATION; DRUG INHIBITION; DRUG ISOLATION; DRUG METABOLISM; DRUG SYNTHESIS; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROXYLATION; IC 50; LIVER MICROSOME; MALE; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RAT; SOLID PHASE EXTRACTION;

ANIMALS; BILE; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; FECES; FICUSIN; KV1.3 POTASSIUM CHANNEL; MALE; METABOLIC DETOXICATION, PHASE I; MICROSOMES, LIVER; POTASSIUM CHANNEL BLOCKERS; RATS; RATS, SPRAGUE-DAWLEY; TOXICITY TESTS, CHRONIC;

RATTUS;

EID: 79951831697     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498254.2010.532886     Document Type: Article

References (28)

1. Azam P, Sankaranarayanan A, Homerick D, Griffey S, Wulff H. (2007). Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic (Pubitemid 46762978)
2. Baririan N, Desager JP, Petit M, Horsmans Y. (2006). CYP3A4 activity in four different animal species liver microsomes using 7-benzyloxyquinoline and HPLC/spectrofluorometric determination. J Pharm Biomed Anal 40:211-214. (Pubitemid 43061240)
3. Baumgart A, Schmidt M, Schmitz HJ, Schrenk D. (2005). Natural furocoumarins as inducers and inhibitors of cytochrome P450 1A1 in rat hepatocytes. Biochem Pharmacol 69:657-667.
4. Beeton C, Barbaria J, Giraud P, Devaux J, Benoliel AM, Gola M, Sabatier JM, Bernard D, Crest M, Béraud E. (2001). Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation. J Immunol 166:936-944. (Pubitemid 32060248)
5. Beeton C, Pennington MW, Wulff H, Singh S, Nugent D, Crossley G, Khaytin I, Calabresi PA, Chen CY, Gutman GA, Chandy KG. (2005). Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Mol Pharmacol 67:1369-1381. (Pubitemid 40410438)
6. Beeton C, Wulff H, Barbaria J, Clot-Faybesse O, Pennington M, Bernard D, Cahalan MD, Chandy KG, Béraud E. (2001). Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc Natl Acad Sci USA 98:13942-13947. (Pubitemid 33116003)
7. Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM, Pennington MW, Kolski-Andreaco A, Wei E, Grino A, Counts DR, Wang PH, LeeHealey CJ, S Andrews B, Sankaranarayanan A, Homerick D, Roeck WW, Tehranzadeh J, Stanhope KL, Zimin P, Havel PJ, Griffey S, Knaus HG, Nepom GT, Gutman GA, Calabresi PA, Chandy KG. (2006). Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci USA 103: 17414-17419. (Pubitemid 44788983)
8. Caffieri S. (2002). Furocoumarin photolysis: chemical and biological aspects. Photochem Photobiol Sci 1:149-157. (Pubitemid 37069723)
9. Cahalan MD, Chandy KG. (2009). The functional network of ion channels in T lymphocytes. Immunol Rev 231:59-87.
10. Chandy KG, Wulff H, Beeton C, Pennington M, Gutman GA, Cahalan MD. (2004). K+ channels as targets for specific immunomodulation. Trends Pharmacol Sci 25:280-289.
11. da Silva VB, Kawano DF, Carvalho I, da Conceição EC, de Freitas O, da Silva CH. (2009). Psoralen and bergapten: in silico metabolism and toxicophoric analysis of drugs used to treat vitiligo. J Pharm Pharm Sci 12:378-387.
12. Daniel WA, Syrek M, Haduch A. (2002). The contribution of cytochrome P-450 isoenzymes to the metabolism of phenothiazine neuroleptics. Eur Neuropsychopharmacol 12:371-377.
13. Elsherbiny ME, El-Kadi AO, Brocks DR. (2008). The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci 11:147-159.
14. Erickson DA, Hollfelder S, Tenge J, Gohdes M, Burkhardt JJ, Krieter PA. (2007). In vitro metabolism of the analgesic bicifadine in the mouse, rat, monkey, and human. Drug Metab Dispos 35:2232-2241. (Pubitemid 350146210)
15. Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG. (1994). Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45:1227-1234. (Pubitemid 24195583)
16. Hill JR. (2003). In vitro drug metabolism using liver microsomes. Current Protocols in Pharmacology. New York: Wiley Inter-science.
17. John BA, Chasseaud LF, Wood SG, Forlot P. (1992). Metabolism of the anti-psoriatic agent 5-methoxypsoralen in humans: comparison with rat and dog. Xenobiotica 22:1339-1351.
18. Koenigs LL, Trager WF. (1998). Mechanism-based inactivation of cytochrome P450 2B1 by 8-methoxypsoralen and several other furanocoumarins. Biochemistry 37:13184-13193. (Pubitemid 28449562)
19. Koenigs LL, Trager WF. (1998). Mechanism-based inactivation of P450 2A6 by furanocoumarins. Biochemistry 37:10047-10061. (Pubitemid 28366359)
20. Logsdon NJ, Kang J, Togo JA, Christian EP, Aiyar J. (1997). A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J Biol Chem 272:32723-32726. (Pubitemid 28023600)
21. Martignoni M, Groothuis GM, de Kanter R. (2006). Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2:875-894. (Pubitemid 44911538)
22. Mays DC, Rogers SL, Guiler RC, Sharp DE, Hecht SG, Staubus AE, Gerber N. (1986). Disposition of 8-methoxypsoralen in the rat: methodology for measurement, dose-dependent pharmacokinetics, tissue distribution and identification of metabolites. J Pharmacol Exp Ther 236:364-373. (Pubitemid 16184227)
23. Monostory K, Tamási V, Vereczkey L, Perjési P. (2003). A study on CYP1A inhibitory action of E-2-(4'-methoxybenzylidene)-1- benzosuberone and some related chalcones and cyclic chalcone analogues. Toxicology 184:203-210. (Pubitemid 36009301)
24. Pereira LE, Villinger F, Wulff H, Sankaranarayanan A, Raman G, Ansari AA. (2007). Pharmacokinetics, toxicity, and functional studies of the selective Kv1.3 channel blocker 5-(4-phenoxybutoxy) psoralen in rhesus macaques. Exp Biol Med (Maywood) 232: 1338-1354. (Pubitemid 350014424)
25. Ropp S, Guy J, Berl V, Bischoff P, Lepoittevin JP. (2004). Synthesis and photocytotoxic activity of new alpha-methylene-gammabutyrolactone- psoralen heterodimers. Bioorg Med Chem 12:3619-3625. (Pubitemid 38746864)
26. Schmitz A, Sankaranarayanan A, Azam P, Schmidt-Lassen K, Homerick D, Hänsel W, Wulff H. (2005). Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Mol Pharmacol 68: 1254-1270. (Pubitemid 41539982)
27. Wulff H, Castle NA, Pardo LA. (2009). Voltage-gated potassium channels as therapeutic targets. Nat Rev Drug Discov 8:982-1001.
28. Zimin PI, Garic B, Bodendiek SB, Mahieux C, Wulff H, Zhorov BS. (2010). Potassium channel block by a tripartite complex of two cationophilic ligands and a potassium ion. Mol Pharmacol 78:588-599.