[Effect of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative 450191-S on rat liver drug-metabolizing enzyme system].
The effect of a new sleep inducer, 450191-S, on the hepatic drug-metabolizing enzyme system was examined using rats and compared with those of nitrazepam and phenobarbital. Cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylation activity determined using liver homogenate and isolated microsomes increased after successive oral administrations of 450191-S, and induction of the enzyme system was observed by administration of 150 approximately 200 mg/kg of the drug for at least 3 approximately 5 days. Normal activity was recovered with withdrawal of the drug for 3 approximately 5 days after induction of the hepatic enzyme system. Administration of higher amounts of 450191-S (200 approximately 600 mg/kg/day) for 3 days caused remarkable increases in the O-dealkylase and UDPGA-glucuronyltransferase activities and cytochrome P-450 and b5 contents. Similar changes in the hepatic enzyme system were observed with administration of nitrazepam (200 approximately 600 mg/kg for 3 days, p.o.) or phenobarbital (10 approximately 40 mg/kg for 3 days, i.p.). We concluded that the inducing activity of 450191-S is almost the same as that of nitrazepam, but weaker than that of phenobarbital. When the hepatic enzyme system was induced by the administration of either 450191-S or phenobarbital, the pentobarbital-induced sleeping time was shortened with increasing doses of the drugs. On the other hand, sleeping time was prolonged by the administration of another type of inducer, beta-naphthoflavone. The results suggest that the inductive pattern of 450191-S is similar to that of phenobarbital.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D004347:Drug Interactions; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009567:Nitrazepam / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D006993:Hypnotics and Sedatives; D014230:Triazoles; D019324:beta-Naphthoflavone; D009567:Nitrazepam; C041075:rilmazafone; D010424:Pentobarbital; D010634:Phenobarbital