Effect of morestan and other substituted quinoxalines on the activities of various rat hepatic mixed-function oxidases

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Abstract
Morestan (6-methyl-2,3-quinoxalinedithiol cyclic-S,S carbonate) and two of its metabolites: methyl-2,3-quinoxalinedithiol and 6-methyl-2,3-quinoxalinedihydroxy were administered to male and female rats by intraperitoneal route for 4 consecutive days (50 mg/ kg/daily). Morestan was also administered by esophageal intubation for 4 days at the dose of 75 mg/kg/daily. After evaluating the pentobarbital sleeping time in the animals on the 5th day, aminopyrineN-demethylase,p-nitroanisoleO-demethylase and aromatic aniline hydroxylase activities and levels of cytochrome P450, proteins and RNA were measured in the microsomal hepatic fraction. Protein and nucleic acid levels were also measured in whole liver. The 3 substances studied caused considerable decreases in activity of certain microsomal enzymes: morestan inhibits some hepatic mixed-function oxidase systems; in females it is more active by peroral administration, and in males by intraperitoneal route. However, 6-methyl-2,3-quinoxalinedithiol is an even more powerful inhibitor of monooxygenase activities both in males and females. 6-methyl-2,3-quinoxalinedihydroxy also decreases activity by microsomal enzymes, but its action is inferior to that of the other two products investigated.