SKF 525-A INHIBITION, INDUCTION, AND 452-NM COMPLEX-FORMATION

Google Scholar
  • 1 January 1976
    • journal article
    • research article
    • Vol. 4  (3) , 244-255
Abstract
After administration of SKF 525-A [proadifen hydrochloride] to rats a portion of the cytochrome P450 in hepatic microsomes was found in the reduced form as a stable complex absorbing at 452 nm. As much as 40% of the total cytochrome P450 was bound in the complexed form after a single administration of SKF 525-A. The addition of potassium ferricyanide (50 .mu.M) to hepatic microsomes from SKF 525-A-treated rats destroyed the complex and made the total cytochrome P450 available for CO binding. At early times after administration of SKF 525-A, when the amount of complexed cytochrome P450 was maximum, mixed-function oxidase activities (p-nitroanisole O-demethylase and norbenzphetamine 455-nm complex formation) were greatly inhibited. Later, as the amount of complexed cytochrome P450 slowly decreased, these mixed-function oxidase activities gradually returned and reached control values in about 48 h. Induction with daily doses of SKF 525-A for several days increased total cytochrome P450 content up to 5-fold, which was more than induction with phenobarbital, but this was evident only after destruction of the complex with ferricyanide. The maximum increase in uncomplexed cytochrome P450 was only 2-fold. Treatment of these microsomal suspensions with ferricyanide enhanced ethylmorphine N-demethylase, p-nitroanisole O-demethylase and norbenzphetamine 455-nm complex formation.