Studies on Drug Metabolism. XIII. Possible Role of Liver Microsomal Cytochrome P-450 in the Oxidative N-Demethylation of p-Sub-stituted Dimethylaniline, N-Methyl-N-alkylaniline and N-Methyl-N-acylaniline Derivatives

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概要

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• N-Demethylation of p-substituted dimethylaniline derivatives, N-methyl-N-alkyl-aniline derivatives and N-methyl-N-acylaniline derivatives was investigated. The rates of N-demethylation of several series of p-substituted dimethylaniline depended upon their lipid solubilities. The more lipid soluble the amine was, the more readily it was demethylated. The p-substituted dimethylanilines of high lipid solubilities revealed small Km and Ks values, whereas those of low lipid solubilities exhibited large Km and Ks values. N-Demethylation activity of the high lipid soluble p-substituted dimethylaniline was intensely stimulated by phenobarbital administration in comparison with that of the low lipid soluble p-substituted dimethylaniline. N-Demethylation of p-substituted dimethyl-aniline of low lipid solubility was inhibited more strongly than that of high lipid solubility by SKF 525-A, but this relation between lipid solubility and inhibitory rate was not observed in carbon monoxide inhibition. The studies on N-demethylation of N-methyl-N-alkylaniline derivatives revealed that the rate of N-demethylation did not always depend on the lipid solubilities of amines. It was suggested that steric hindrance about the nitrogen atom interfered with N-demethylation of N-methyl-N-alkylaniline derivatives. In the studies on N-demethylation of N-methyl-N-acylaniline derivatives, the difference of N-demethylation rate between N-methyl-N-propyonylaniline and N-methyl-N-benzoyl-aniline seemed to depend on the spectral change per P-450 rather than lipid solubility.

• 社団法人日本薬学会の論文
• 1972-04-25

著者

• 北川 晴雄

  Faculty of Pharmaceutical Sciences, Chiba University

• 北田 光一

  Faculty Of Pharmaceutical Sciences University Of Chiba

• 堀江 透

  Faculty of Pharmaceutical Sciences, University of Chiba

• 北川 晴雄

  Faculty Of Pharmaceutical Sciences Chiba University

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