Effects of perinatal exposure of Wistar rats to l-alpha-acetylmethadol.HCl on hepatic microsomal mixed-function oxidase enzyme activity in the adult.
I-alpha-Acetylmethadol (LAAM) was administered via the drinking water to female Wistar rats throughout pregnancy and lactation. Controls were pair-fed and watered. After weaning, pups received lab chow and water ad lib. until maturity. The apparent KM and Vmax were determined for benzo[a]pyrene hydroxylase (BPH), aminopyrine N-demethylase (AP), ethylmorphine N-demethylase (ET) and aniline hydroxylase (AN) from the hepatic microsomal fraction of the mature male and female offspring. The dose of LAAM administered was low enough to produce no symptomatology. In the adult male, pre- and neonatal exposure to LAAM resulted in decreases in KM for AP and Vmax for AN, and increase in the KM and Vmax for BPH. For the female, LAAM produced an increase in KM for AP and a decrease in Vmax for ET and BPH. That is, long-term changes occurred in the enzyme parameters measured; the direction of the changes were sex- and substrate-dependent.
D000818:Animals; D005260:Female; D007700:Kinetics; D008297:Male; D008691:Methadone / Q000031:analogs & derivatives*; D008692:Methadyl Acetate / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains
D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D008692:Methadyl Acetate; D008691:Methadone