l-alpha-Acetylmethadol administration to lactating rat dams. Effect on hepatic aniline hydroxylase and ethylmorphine N-demethylase activities in rat pups.
l-alpha-Acetylmethadol (LAAM) was administered to lactating rat dams, and subsequent effects on hepatic drug-metabolizing enzymes of their offspring were assessed. Dams were given LAAM or a control solution in their drinking water following parturition and throughout lactation. Hepatic ethylmorphine-N-demethylase (EMDM) and aniline hydroxylase (AH) activities, as well as cytochrome P-450 content, were determined in the offspring at 21-23 days of age, or following sexual maturation (61-64 days). LAAM induced AH and EMDM activities, as well as cytochrome P-450 content in both male and female 21-23-day-old pups compared to controls; these differences were not observed at 61-64 days of age. In addition, normal sex-related differences in EMDM activity were apparent at 61-64 days of age. These results demonstrate the LAAM administration to lactating dams causes hepatic metabolic induction in the sexually immature rat, suggesting that LAAM and/or its metabolites passed to the pups via the milk. These changes, induced by LAAM administered via lactation, are reversible and do not interfere with the normal development of sex-dependent differences in hepatic EMDM activity observed in rats following sexual maturation.
D000815:Aniline Hydroxylase / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D005260:Female; D007774:Lactation; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008691:Methadone / Q000031:analogs & derivatives*; D008692:Methadyl Acetate / Q000494:pharmacology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D012737:Sex Factors
D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase; D008692:Methadyl Acetate; D008691:Methadone