TY - JOUR T1 - Studies on Hepatic Microsomal <em>N</em>- and <em>O</em>-Dealkylation of Morphine Analogues JF - Molecular Pharmacology JO - Mol Pharmacol SP - 502 LP - 509 VL - 4 IS - 5 AU - W. J. GEORGE AU - T. R. TEPHLY Y1 - 1968/09/01 UR - http://molpharm.aspetjournals.org/content/4/5/502.abstract N2 - N-Dealkylation of ethylmorphine and O-dealkylation of norcodeine were studied in hepatic microsomes from male rats. Both reactions appeared to be equally sensitive to carbon monoxide, and the inhibitions produced by CO were light-reversible. Chronic phenobarbital administration stimulated the N-dealkylation of ethylmorphine but had no effect on the O-dealkylation of norcodeine in hepatic microsomes. Hexobarbital produced a competitive inhibition of ethylmorphine oxidation but effected an inhibition of norcodeine oxidation that was not competitive. Ethylmorphine N-dealkylation was more labile to heat treatment than was norcodeine O-dealkylation. Fasting-adapted rats that received food for 12 hr out of each 48-hr period for 28 days yielded hepatic microsomes which displayed an increased ethylmorphine oxidation with no change in norcodeine oxidation and no change in hepatic cytochrome P-450 content. These studies indicate different rate-controlling events in the oxidation of ethylmorphine and norcodeine, although each reaction depends upon the participation of cytochrome P450. ACKNOWLEDGMENTS This research was supported in part by an institutional grant (NSF 89) and in part by United States Public Health Service Research Grant AM-12168. ER -