L-alpha-acetylmethadol-induced tissue alterations in mice.

Single oral dosages of the synthetic narcotic analgesic, L-alpha-acetylmethadol (LAAM) increased serum glutamic-pyruvic transaminase (SGPT) levels throughout a two-day observation period and produced a persistent depletion of hepatic and renal glutathione (GSH) levels. These LAAM-induced changes demonstrated dose- and time-dependence within that dosage range producing mortality. Histological evaluation of livers from LAAM-treated mice revealed cytoplasmic and nuclear changes in centrilobular hepatocytes. Interestingly, neither the LAAM-induced histopathological changes nor the depression of hepatic GSH were altered by the induction of hepatic metabolism following pretreatment with either phenobarbital or 3-methylcholanthrene; however, the induction of hepatic drug metabolism did abate the four-day mortality and SGPT elevations.