Metabolism of ethers in the rabbit. 2. Nuclear-substituted anisoles

Abstract

The fate of some substituted anisoles in the rabbit was studied and over 74% of the dose of each compound was accounted for. The chief metabolites of m- and p-nitro, p-chloro-, p-methoxy- and p-cyano-anisoles are the corresponding phenols formed by demethylation and excreted mainly as conjugates of glucuronic and sulfuric acids. Dihydric phenols were detected as metabolites of m- and p-nitro, p-cyano- and p-chloro-anisoles. The greater part of a dose of p-methylanisole was oxidized to anisic acid; about 27% was demethylated and excreted, mainly as p-cresol. p-Methoxyphenol was excreted mainly conjugated with glucuronic and sulfuric acids, but partly demethylated to quinol. Anisic acid was excreted mainly as ester glucuronide and anisuric acid. Velocity constants for the demethylation of substituted anisoles range from 0.08 to 0.24 hour-1. Some substituted anisoles are demethylated by incubation with rabbit-liver slices.