Inhibition of nasal and liver cytochrome P-450 mono-oxygenases by dioxolanes.
1. A series of six alkyl-substituted dioxolanes were studied for their inhibitory effects on mono-oxygenase activities in vitro with nasal and hepatic microsomes from rats and rabbits. 2. Carbon monoxide binding and hexamethylphosphoramide (HMPA) N-demethylase activity were most susceptible to inhibition by the test compounds. 3. Inhibition of HMPA N-demethylase activity in both nasal and liver microsomes increased with lipophilicity of the inhibiting compound. In olfactory mucosa, the bulk of the substituent at the 4-position also seemed to have an effect on inhibition. 4. Mono-oxygenase activity in the nasal mucosa was inhibited more readily than that in the liver.
Petridou-Fischer
J
J
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
Dahl
A
A
D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D004148:Dioxolanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D009666:Nose / Q000201:enzymology*; D009928:Organ Specificity; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013329:Structure-Activity Relationship
D004148:Dioxolanes; D004149:Dioxoles; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases