Larry A. Rogers

The effects of norepinephrine treatment on drug metabolism by liver microsomes from rats

Abstract A single, large intraperitoneal injection of norepinephrine has little effect on the hepatic microsomal metabolism of hexobarbital, aminopyrine, or aniline, though hepatic glycogen levels are markedly depressed for at least 12 hr. Repeated injections of norepinephrine will depress both hepatic glycogen and the microsomal drug metabolisms studied. These effects are at least partially reversible when injections or norepinephrine are stopped. Phenoxybenzamine and dihydroergotamine, given i.p., can block the effects of norepinephrine on hepatic glycogen, but cannot be said to block effects of the catecholamine on microsomal drug metabolism because these adrenolytic drugs (and also dichloroisoproterenol) have a direct inhibitory effect on the hepatic drug metabolisms studied. The inhibition of the microsomal metabolism of hexobarbital and aminopyrine by phenoxybenzamine and dihydroergotamine is of the same order as that seen with SKF 525 (β-diethylaminoethyldiphenylpropyl acetate) and is the subject of further investigation.

The effects of SKF 525-A on hepatic glycogen and rate of hepatic drug metabolism.

Abstract The level of hepatic glycogen and rates of certain drug metabolisms were studied after administration of SKF 525-A (β-diethylaminoethyl diphenylpropyl acetate HCl) to adult rats. SKF 525-A inhibits hepatic drug metabolism within 1 hr, and a significant effect is seen up to 24 hr after administration. SKF 525-A lowers hepatic glycogen to a minimum level in 8 to 12 hr. The recovery of hepatic glycogen and rate of hepatic drug metabolism to control values occurs at the same time after administration of SKF 525-A. The effects of SKF 525-A on certain enzymes of hepatic glycogenesis and glycogenolysis were also studied.

Effect of Acute Alpha-Naphthylisothiocyanate Administration on Hepatic Microsomal Drug Metabolism in the Mouse.∗

Summary When 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.