STUDIES ON N-DEMETHYLATION AND O-DE-ETHYLATION OF ETHYLMORPHINE BY HEPATIC MICROSOMES FROM MALE RATS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 5  (1) , 9-14
Abstract
The microsomal dealkylation of 3-O-[1''-14C]ethylmorphine was investigated by measuring HCHO colorimetrically and [1-14C]acetaldehyde radiometrically. The KM for the O-de-ethylation is 57 .mu.M, which is quite close to the KS (71 .mu.M) for the type l binding of ethylmorphine in similar preparations. The KM for N-demethylation was 250 .mu.M. The N-demethylation was stoichiometric with the stimulation of both NADPH-cytochrome P-450 reductase and NADPH oxidase; the sum of the N-demethylation and O-de-ethylation was significantly greater, suggesting that the O-de-ethylase activity does not involve stimulation of either of these 2 activities. Induction with phenobarbital increased N-demethylation 118% but did not affect O-de-ethylation. Finally, D2O inhibited the N-demethylase more than the O-de-ethylase.