Induction of hepatic cytochrome P-450c-dependent monooxygenase activities by dantrolene in rat.
The effect of dantrolene sodium, a skeletal muscle relaxant, on drug metabolizing enzymes has been investigated after treatment of rats with a dose of 200 mg/kg for five days. We observed an induction of cytochrome P-450c and epoxide hydrolase in immunoassays and activities. An enhancement of the UDP-glucuronosyltransferase (GT1) activity was observed. We also reported a decrease of both liver cytochrome P-450 content and microsomal cytochrome P-450b dependent N-demethylation activities. On the other hand, the binding of dantrolene on microsomal cytochrome P-450 produced a type I difference spectrum, these data were obtained with liver microsomal cytochrome P-450c induced by 3-methylcholanthrene.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D003620:Dantrolene / Q000494:pharmacology*; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010105:Oxygenases / Q000096:biosynthesis*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D014453:Glucuronosyltransferase; D004851:Epoxide Hydrolases; D003620:Dantrolene; D010634:Phenobarbital