Inhibition of nasal and liver cytochrome P-450 mono-oxygenases by dioxolanes

Abstract

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.