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8645252 
Journal Article 
INFLUENCE OF DRUGS AND CHEMICALS UPON HEPATIC ENZYMES AND PROTEINS .1. STRUCTURE-ACTIVITY RELATIONSHIP BETWEEN VARIOUS BARBITURATES AND MICROSOMAL-ENZYME INDUCTION IN RAT-LIVER 
Adachi, Y; Yamamoto, T 
1976 
Yes 
Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 
Elsevier 
25 
6 
663-668 
English 
6036 
WOS:A1976BK55200009 
The effect of phenobarbital, three N-phenylbarbiturates and three N-cyclohexylbarbiturates on microsomal protein content, cytochrome P-450, cytochrome b5, aniline hydroxylase, aminopyrine demethylase, p-nitrophenol-glucuronyltransferase and the ultrastructure of hepatic cells in rat liver were studied to elucidate the influence of barbiturate structure on enzyme-inducing activity. Smooth endoplasmic reticulum increased after administration of phenobarbital, phetharbital or bucolome. Phenobarbital and phetharbital, especially phenobarbital, induced cytochrome P-450 and glucuronyl-transferase. On the other hand, the other barbiturates showed little enzyme-inducing activity. From these results, the type and spatial position of barbiturate substituents are considered important for hepatic microsomal enzyme induction. Aniline hydroxylase and aminopyrine demethylase activities changed coincidentally with cytochrome P-450 content in almost all rat livers. However, quantitative agreement of the changes in cytochrome P-450 content and drug-metabolizing activity could not be obtained, suggesting the possibility of substrate inhibition or of intrinsic inhibitors in the microsomal fraction. Bucolome, one of the N-cyclohexylbarbiturates, has been reported to be effective in the reduction of serum unconjugated bilirubin level in Gilbert's syndrome. However, in. spite of the increased smooth endoplasmic reticulum, there was a reduction in the microsomal protein content, cytochrome P-450 and glucuronyltransferase after bucolome administration. This would seem to indicate that the serum bilirubin-reducing mechanism of bucolome is different from that of phenobarbital and phetharbital. © 1976.