Differences between induction effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene and phenobarbitone.
The inductive effects of phenobarbitone (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) were compared in C57BL/6J mice. Induction parameters included six substrates: ethylmorphine (EM), benzphetamine (Bph), biphenyl, ethoxycoumarin (EtoC), pentoxyresorufin and dichloro-p-nitroanisole (DPNA). In order to validate this descriptive approach the comparison was extended to diazepam, rifampicin, warfarin, and pregnenolone-16 alpha-carbonitrile (PCN). All inducers were clearly distinguishable from each other. Warfarin was similar to PB, rifampicin was similar to PCN. TCPOBOP differed significantly from PB in relative liver weight, cytochrome P-450 content of liver microsomes, EM-, Bph- and DPNA-demethylations, biphenyl-hydroxylations, EtoC de-ethylation and absorption maximum of reduced CO-cytochrome P-450. TCPOBOP, as an inducer, was less "specific" than PB: total metabolic rates were excessively increased due to microsomal protein (1.5 times) and cytochrome P-450 (4 times) augmentation, whereas cytochrome P-450-related metabolic rates were less increased than those after PB. Thus TCPOBOP does not seem to be as similar to PB as was suggested in the first description of its inducing potency.
Heubel
F
F
Institut für Pharmakologie und Toxikologie Philipps-Universität, Marburg/Lahn, Federal Republic of Germany.
Reuter
T
T
Gerstner
E
E
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003975:Diazepam / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology*; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology
D011725:Pyridines; D011285:Pregnenolone Carbonitrile; D014859:Warfarin; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D003975:Diazepam; D012293:Rifampin; D010634:Phenobarbital