Depression of the hepatic cytochrome P-450 mono-oxygenase system by administered tilorone (2,7-bis(2-(diethylamino)ethoxy)fluoren-9-one dihydrochloride).
The oral administration of the antiviral agent, tilorone-HCl (50 mg/day for 4 days) to rats caused losses of hepatic microsomal ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase and aniline hydroxylase activities of 50, 44 and 22%, respectively. Microsomal levels of cytochrome P-450 and NADPH-cytochrome c reductase were lowered by 40 and 20% respectively, but levels of cytochrome b5 and NADH-cytochrome c reductase remained unchanged. After a single oral dose of tilorone-HCl (50 mg/kg) a loss of 38% of the microsomal cytochrome P-450 and 25% of the ethylmorphine N-demethylase activity was observed within 24 hr; recovery was complete within 8 to 10 days. Hexobarbital sleeping times and blood levels were elevated after tilorone administration (20 or 50 mg/kg/day for 4 days). In vitro, tilorone-HCl showed no inhibitory effect on microsomal drug metabolism nod did it affect the cytochrome P-450 content of the microsomes. The rate of incorporation of  delta-amino(3H)levulinic acid into cytochrome P-450 was not affected by tilorone-HCl.
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D001665:Binding Sites; D001835:Body Weight; D065607:Cytochrome P-450 Enzyme Inhibitors; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005449:Fluorenes / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009929:Organ Size; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D051381:Rats; D013053:Spectrophotometry; D013994:Tilorone / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D005449:Fluorenes; D010105:Oxygenases; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D013994:Tilorone