DEMETHYLATION STUDIES .6. INHIBITION OF HEPATIC MICROSOMAL OXYGENATION BY 2,4-DICHLORO(6-PHENYLPHENOXY)ETHYLAMINE AND RELATED COMPOUNDS

A series of o-phenylphenoxyethylamines has been studied as inhibitors of microsomal drug oxidation. Optimum activity resided in primary amines having an o-chloro substituent and unbranched ethylene chain. 2,4-Dichloro( 6-phenylphenoxy)ethylamine (1, DPEA) was shown to be a particularly effective inhibitor of the dealkylation of a variety of drugs. In the intact rat, 1 inhibited the demethylation of butynamine and imipramine but not of propoxyphene or p-bromoanisole. Compound 1 prolonged hexobarbital and ethinamate sleeping time in mice and in dogs. When fed chronically, 1 was a weak stimulant of hepatic microsomal oxygenase. © 1969, American Chemical Society. All rights reserved.