Inhibition of rabbit nasal and hepatic cytochrome P-450-dependent hexamethylphosphoramide (HMPA) N-demethylase by methylenedioxyphenyl compounds.
Eighteen methylenedioxyphenyl (MDP) compounds, including some commonly inhaled by people, were tested for the ability to inhibit rabbit nasal microsomal cytochrome P-450-dependent hexamethylphosphoramide (HMPA) N-demethylase. For comparison, liver microsomes were also used. Nasal cytochrome P-450 from rabbits metabolized MDP compounds to form cytochrome P-450-metabolite (P-450-MI) complexes as indicated by difference spectra in the Soret region. Several of the MDP compounds were potent inhibitors of nasal P-450-dependent N-demethylase. If inhibition of nasal P-450 also occurs in vivo after inhibiting MDP compounds are inhaled, the metabolism of concurrently or subsequently inhaled compounds may be altered.
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology; D052117:Benzodioxoles; D002273:Carcinogens / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003640:Dealkylation; D004149:Dioxoles / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009666:Nose / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011817:Rabbits; D012451:Safrole / Q000494:pharmacology
D001547:Benzaldehydes; D052117:Benzodioxoles; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D004149:Dioxoles; D010636:Phenols; C025583:sesamol; D010089:Oxidoreductases, N-Demethylating; C044713:hexamethylphosphoramide N-demethylase; C005454:piperonal; D010882:Piperonyl Butoxide; D012451:Safrole; C015959:isosafrole