Effect of acute alpha-naphthylisothiocyanate administration on hepatic microsomal drug metabolism in the mouse.

Abstract

SummaryWhen alpha-naphthylisothiocyanate was administered orally to mice, the hepatic microsomal drug metabolizing activity for hexobarbital and aniline was significantly depressed 2 hours after treatment; the inhibition persisted for 9 days. Chlorpromazine metabolism was not affected. Phenylisothiocyanate and beta-naphthylisothiocyanate also inhibited some drug metabolizing pathways at 2 hours, but were neither as effective, nor as persistent, as alpha-naphthylisothiocyanate. Alpha-naphthylisothiocyanate and phenylisothiocyanate added directly to hepatic microsomes inhibited hexobarbital metabolism in concentrations as low as 10-5 M. Chlorpromazine metabolism was affected only when the concentrations were 10-3 M.