TY - JOUR T1 - Studies on the N-demethylation and O-de-ethylation of ethylmorphine by hepatic microsomes from male rats. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 9 LP - 14 VL - 5 IS - 1 AU - J A Thompson AU - J L Holtzman Y1 - 1977/01/01 UR - http://dmd.aspetjournals.org/content/5/1/9.abstract N2 - On the basis of inhibition studies of the dealkylation of morphine and norcodeine, George and Tephly concluded that O-dealkylation and N-dealkylation are catalyzed by different enzymes. We have examined the microsomal dealkylation of 3-O-[1'-14Clethylmorphine by measuring HCHO colorimetrically and [1-14C]acetaldehyde radiometrically. We find that the KM for the O-de-ethylation is 57 muM, which is quite close to the KS(71 muM) for the type I binding of ethylmorphine in similar preparations. On the other hand, the KM for N-demethylation was 250 muM. Further, the N-demethylation was stoichiometric with the stimulation of both NADPH-cytochrome P-450 reductase and NADPH oxidase, whereas 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 two activities. Induction with phenobarbital increaesed N-demethylation 118% but did not affect O-de-ethylation. Finally, D2O inhibited the N-demethylase more than the O-de-ethylase. ER -