Inhibitors of Hepatic Mixed Function Oxidases I. The Metabolism of 2,6-Dihydroxy-, 2-Hydroxy-6-methoxy- and 2,6-Dimethoxyaeetophenones

Abstract

1. 2,6-Dihydroxyacetophenone, its mono- and di-methyl ethers are inhibitors of hepatic mixed function oxidases. The dimethyl ether is a competitive inhibitor of aminopyrine demethylase with the others displaying mixed kinetics. The metabolism of all three ketones has been studied.

2. 2,6-Dihydroxyacetophenone is excreted unchanged and as conjugates.

3. 2-Hydroxy-6-methoxyacetophenone is largely excreted unchanged and conjugated but small amounts of the 3- and 5-hydroxylated derivatives are formed.

4. 2,6-Dimethoxyacetophenone is demethylated to 2-hydroxy-6-methoxyacetophenone. In addition 3-hydroxy-2, 5-dimethoxyacetophenone and 2,3-dihydroxy-6-methoxyacetophenone were identified as metabolites.

5. Quantitative data on the excretion of metabolites were obtained with ¹⁴C-labelled ketones.