Action of oxatomide on the hepatic microsomal enzyme system. Effect of the monoxygenase and peroxidase activity of P-450 on drug N-demethylations.

The effect of oxatomide and astemizole on the rat's response to zoxazolamine was examined. It was found that the former increases the body's resistance to zoxazolamine. The effect of the pretreatment with oxatomide, pregnenolone-16 alpha-carbonitrile or tocopherol acetate on the in vitro N-demethylation of ethylmorphine, aminopyrine, the reduction of p-nitrobenzoic acid, P-450 and hepatic protein content was determined. It was found that 1) oxatomide increased N-demethylation and the content of both P-450 and hepatic protein, 2) PCN increased all the examined parameters and 3) tocopherol acetate induced only the ethylmorphine N-demethylation. The role of P-450 as a monoxygenase or as a peroxidase under these experimental conditions is discussed.