Summary
Apparent kinetic parameters Vmax and KM have been measured for the oxidative N-demethylation of twelve para-substituted N, N-dimethylanilines catalysed by rat liver microsomes. Vmax was enhanced by pretreatment of the rats with phénobarbital, whereas pretreatment with β-naphthoflavone gave no appreciable enhancement. In the case of phénobarbital pretreatment the kinetic parameters could be expressed in terms of lipophilic and electronic effect of the substituents. Kinetic parameters from control and β-naphthoflavone microsomes gave no statistically meaningful correlation.
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References
Gorrod J.W. (1978):Biological Oxidation of Nitrogen, Elsevier/North Holland, Biomedical Press, New York.
Archakov A.I., Karuzina I.I., Tveritinov V.N. and Kokauwa I.S. (1974):Biochem. Pharm., 23, 1053.
Willi P. and Bickel M.H. (1973): Liver metabolic reactions: Tertiary amine N-dealkylation, tertiary amine N-oxidation, N-oxide reduction, and N-oxide N-dealkylation. II N,N-dimethylaniline.Arch. Biochem. Biophys., 156, 772–779.
Galliani G., Rindone B. and Beltrame P.L. (1976): Kinetics of the oxidation of some meta and para-substituted N, N-dimethylanilines with lead tetra-acetate.J. Chem. Soc. Perkin Trans. 2, 1803–1807.
Galliani G. and Rindone B. (1981): Electronic factors and lipophilicity in the horseradish peroxidase-catalysed oxidation of N, N-dialkylanilines with hydrogen peroxide and oxygen.Bioorganic Chemistry, 10, 283–289.
Galliani G. and Rindone B. (1983): The intervention of oxygen in the oxidation of N, N-dimethylanilines with Fenton’s reagent.Gazzetta Chimica Italiana, 113, 207–211.
Griffin B.W., Davis D.K. and Bruno G.V. (1981): Electron paramagnetic Resonance study of the oxidation of N-methyl-substituted aromatic amines catalysed by hemeproteins.Bioorganic Chemistry, 10, 342–355.
Kadlubar F.F., Morton K.C. and Ziegler D.M. (1973): Microsomal-catalysed hydroperoxide-dependent C-oxidation of amines,Biochem. Biophys Res. Comm., 54, 1255–1261.
Kato R. and Takayanagi M. (1966): Differences among the action of phénobarbital, methylcholanthrene and male sex hormone on microsomal drug-metabolizing enzyme systems of rat liver.Jap. J. Pharmac, 16, 380–390.
Lowry O.H., Rosebrough N.J., Farr A.L. and Randall R.J. (1951): Protein measurement with the folin phenol reagent,J. Biol. Chem., 193, 265–275.
Nash T. (1953): The colorimetric estimation of formaldehyde by means of the Hantzsch reaction.Biochem. J., 55, 416–421.
Lenk W. (1976): Application and interpretation of kinetic analyses from the microsomal drug metabolising oxygenases.Biochem. Pharm., 25, 997–1005.
Schmidt H.L., Möller M.R. und Weber N. (1973): Über den einfluss von substituenten auf die mikrosomale entalkylierung aromatischer N-, O- und S-alkylverbindungen.Biochem. Pharmac, 22, 2989–2996.
Hansch C., Leo A., Unger S.H., Kim K.H., Nikaitani D. and Lien E.J. (1973). “Aromatic” substituent constants for structure-activity correlations.J. Med. Chem., 16, 1207–1216.
Cohen S.G., Parola A. and Parsons G.H. Jr. (1973): Photoreduction by amines.Chem. Rev., 73, 141–161.
Lindsay-Smith J.R. and Audeh C.A. (1971): Amine oxidation. III. Oxidation of aralkyl tertiary amines with alkaline potassium hexacyanoferrate (III).J. Chem. Soc. (B), 1741–1744.
Davis G.T., Demek M.M. and Rosenblatt D.H. (1972): Oxidations of amines. X. Detailed kinetics in the reaction of chlorine dioxide with triethylenediamine.J. Amer. Chem. Soc., 94, 3321–3325.
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Galliani, G., Rindone, B., Dagnino, G. et al. Structure reactivity relationships in the microsomal oxidation of tertiary amines. European Journal of Drug Metabolism and Pharmacokinetics 9, 289–293 (1984). https://doi.org/10.1007/BF03189678
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DOI: https://doi.org/10.1007/BF03189678