Induction of rat-hepatic microsomal cytochrome P-450 and aryl hydrocarbon hydroxylase by 1,3-benzodioxole derivatives.
Several 1,3-benzodioxoles (BD) and related compounds were studied in relation to their ability to generate metabolite complexes with hepatic cytochrome P-450 following administration in vivo to rats. BD derivatives that formed stable metabolite complexes with cytochrome P-450 were considerably more effective inducers of cytochrome P-450 and aryl hydrocarbon (benzo[alpha]pyrene) hydroxylase (AHH) activity than derivatives that did not form stable complexes. Linear regression analysis showed that AHH activity was well correlated (r = 0.980) with total (i.e. complexed plus uncomplexed) cytochrome P-450 content and was not correlated with levels of uncomplexed cytochrome P-450. Aminopyrine N-demethylase (APDM) activity in hepatic microsomes from rats treated with 1,3-benzodioxoles was moderately correlated in a linear relationship with uncomplexed levels of cytochrome P-450 and not with total cytochrome P-450.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004149:Dioxoles / Q000378:metabolism* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D004149:Dioxoles; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; C040539:1,3-benzodioxole