Relatively little is known of the metabolism of the aliphatic hydroxylamines that are the primary metabolites of amines in some species. Whole animal studies indicate that only a portion of the administered dose is recovered as identifiable metabolites. The losses in recovery could reflect unknown metabolites or metabolites with long half-lives of elimination. Although these metabolites could constitute a small proportion of the administered dose, they could accumulate with chronic treatment because of their long stay in the body and cause deleterious effects. This project will elucidate pathways of metabolism of the N-hydroxy metabolites of amphetamine and phentermine. The conversion of these hydroxylamines to the nitroso and nitro state as well as their subsequent metabolism will be examined in vitro with liver preparations from rat and rabbit. Results obtained thus far indicate that the oxidation of N-hydroxyphentermine is a chemical reaction effected by O2 negative or O2 double negative generated by cytochrome P-450. The oxidation of N-hydroxy-amphetamine appears to be independent of cytochrome P-450 and results in phenylacetone oxime formation. The biochemical details for these reactions are currently being investigated. The formation of benzoic acid is also being investigated to determine the role of N-oxidation in the formation of this compound.