Microsomal catalyzed N-hydroxylation of guanabenz and reduction of the N-hydroxylated metabolite: Characterization of the two reactions and genotoxic potential of guanoxabenz

Chemical Research in Toxicology

Volumn 9, Issue 4, 1996, Pages 682-688

  Clement, Bernd ^a   Demesmaeker, Mark ^a   Linne, Sabine ^a  

^a UNIVERSITY OF KIEL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ORYCTOLAGUS CUNICULUS;

ALPHA 2 ADRENERGIC RECEPTOR BLOCKING AGENT; CYTOCHROME P450; DRUG METABOLITE; GUANABENZ; GUANABENZ ACETATE; GUANOXABENZ; PRODRUG; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE;

AMES TEST; ANIMAL TISSUE; ARTICLE; CELL FRACTIONATION; CHEMICAL REACTION; CONTROLLED STUDY; DRUG DETOXIFICATION; DRUG HYDROXYLATION; DRUG OXIDATION; DRUG TRANSFORMATION; FEMALE; GENOTOXICITY; HUMAN; HUMAN TISSUE; LIVER CYTOSOL; LIVER MICROSOME; MALE; MUTAGENICITY; NONHUMAN; RABBIT; SWINE;

ADRENERGIC ALPHA-AGONISTS; ANIMALS; ANTIHYPERTENSIVE AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; FEMALE; GUANABENZ; HUMANS; HYDROXYLATION; MALE; MASS SPECTROMETRY; METABOLIC DETOXICATION, DRUG; MICROSOMES, LIVER; MUTAGENICITY TESTS; NAD; NADP; NADPH-FERRIHEMOPROTEIN REDUCTASE; OXIDATION-REDUCTION; RABBITS; SPECTROPHOTOMETRY, ULTRAVIOLET; SWINE;

EID: 0029967158     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx9502047     Document Type: Article

References (27)

1. Baum, T., Shropshire, A. T., Rowles, G., van Pelt, R., Fernandez, S. P., Eckfeld, D. K., and Gluckman, M. I. (1970) General pharmacologic actions of the antihypertensive agent 2,6-dichlorobenzylidene-aminoguanidine acetate (WY-8679). J. Pharmacol. Exp. Ther. 171, 276-287.
2. Holmes, B., Brogden, R. N., Heel, R. C., Speight, T. M., and Avery, G. S. (1983) Guanabenz a review of its pharmacodynamic properties and therapeutic efficacy in hypertension. Drugs 26, 212-229.
3. Boyajy, L. D., Manning, R., McIntosh, R., Fix, K., Herzig, M., and Trapold, J. H. (1969) Hypotensive and bradycardic effects of 1-(2,6-dichlorobenzalamino)-3-hydroxyguanidine hydrochloride. Fed. Proc. 28, 738, Abstr. 2683.
4. Shearer, C. M. (1986) Guanabenz acetate. Anal. Profiles Drug. Subst. 15, 319-336.
5. 14C-guanabenz in patients with essential hypertension. Clin. Pharmacol. Ther. 27, 44-52.
6. Clement, B., Jung, F., and Pfundner, H. (1993) N-hydroxylation of benzamidine to benzamidoxime by a reconstituted cytochrome P450 oxidase system for rabbit liver: Involvement of cytochrome P450 2C3. Mol. Pharmacol. 43, 335-342.
7. Clement, B., and Kunze, T. (1993) The in vitro oxygenation of N,N′-diphenylguanidines. Xenobiotica 23, 155-167.
8. Clement, B., Schultze-Mosgau, M. H., Richter, P. H., and Besch, A. (1994) Cytochrome P450 dependent N-hydroxylation of an aminoguanidine (amidinohydrazone) and microsomal retroreduction of the N-hydroxylated product. Xenobiotica 24, 671-688.
9. Clement, B., Schultze-Mosgau, M. H., and Wohlers, H. (1993) Cytochrome P450 dependent N-hydroxylation of a guanidine (debrisoquine), microsomal catalyzed reduction and further oxidation of the N-hydroxyguanidine metabolite to the urea derivative: similarity with the oxidation of arginine to citrulline and NO. Biochem. Pharmacol. 46, 2249-2267.
10. Clement, B., Schmezer, H., Weber, J. R., Schlehofer, J. R., Schmitt, S., and Pool, B. L. (1988) Genotoxic activities of benzamidine and its N-hydroxylated metabolite benzamidoxime in S. typhimurium and in mammalian cells. J. Cancer Res. Clin. Oncol. 114, 363-368.
11. Kling, L., Legrum, W., and Netter, K. J. (1985) Induction of liver cytochrome P450 in mice by warfarin. Biochem. Pharmacol. 34, 85-91.
12. Yasukochi, Y., and Masters, B. B. S. (1976) Some properties of a detergent-solubilized NADPH-cytochrome C (cytochrome P450) reductase purified by biospecific affinity chromatography. J. Biol. Chem. 251, 5337-5344.
13. Omura, T., and Sato, R. (1964) The carbon monoxide-binding pigment of liver microsomes. J. Biol. Chem. 239, 2370-2378.
14. Gornall, A. G., Bardawill, C. J., and David, M. M. (1949) Determination of serum proteins by means of the biuret reaction. J. Biol. Chem. 177, 751-766.
15. Maron, D. M., and Ames, B. N. (1983) Revised methods for the Salmonella mutagenicity test. Mutat. Res. 113, 173-215.
16. Yahagi, T., Nagao, M., Seino, Y., Matsushima, T., Sugimura, T., and Okada, M. (1977) Mutagenicities of N-nitrosamines on salmonella. Mutat. Res. 48, 121-130.
17. Miyamoto, A., Soda, Y., Mori, I., Yokoyama, N., Horisaka, K., Shichino, F., Shimada, A., Kashima, K., Kataoka, T., and Tatsumi, H. (1982) Metabolic fate of guanabenz acetate. Metabolites of guanabenz acetate in rats. Iyakuhin Kenkyu 13, 1214-1230.
18. Kadlubar, F. F., McKee, E. M., and Ziegler, D. M. (1973) Reduced pyridine nucleotide-dependent N-hydroxy amine oxidase and reductase activities of hepatic microsomes. Arch. Biochem. Biophys. 156, 46-57.
19. Kadlubar, F. F., and Ziegler, D. M. (1974) Properties of a NADH-dependent N-hydroxy amine reductase isolated from pig liver microsomes. Arch. Biochem. Biophys. 162, 83-99.
20. Uhlen, S., and Wikberg, E. S. (1991) Delineation of three pharmacological subtypes of α2-adrenoceptor in the rat kidney. Br. J. Pharmacol. 104, 657-664.
21. 2-receptors. Drug Dev. Res. 3, 91-99.
22. Atlas, D. (1991) Clonidine-displacing substance (CDS) and its putative imidazoline receptor. Biochem. Pharmacol. 41, 1541-1549.
23. Molderings, G. J., Göthert, M., Christen, O., and Schäfer, S. G. (1993) Imidazolinrezeptoren und Blutdruckregulation. Dtsch. med. Wschr. 118, 953-958.
24. Palmer, R. J. M., Ferrige, A. G., and Moncada, S. (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327, 524-526.
25. Ferguson, L. R., and Sundberg, R. J. (1991) Petite mutagenesis in Saccharomyces cerevisiae by a series of bis-cationic trypanocidal drugs. Antimicrob. Agents Chemother. 35, No. 11, 2318-2321.
26. Ferguson, L. R., and Baguley, B. C. (1983) Induction of petite mutants in yeast by nonintercalative DNA-binding antitumor agents. Eur. J. Cancer Clin. Oncol. 19, No. 11, 1575-1583.
27. Claxton, L. D., Allen, J., Auletta, A., Mortelmans, K., Nestmann, E., and Zeiger, E. (1987) Guide for the Salmonella typhimurium/ mammalian microsome tests for bacterial mutagenicity. Mutat. Res. 189, 83-91.