The metabolism of tertiary amines

Abstract

The metabolism of tertiary amines is mediated primarily by cytochrome P-450 and MFAO, leading to alpha-C oxidation and N-oxidation, respectively. We have discussed how lipophilicity, basicity, steric hindrance, and stereochemistry can effect the outcome of metabolism as well as species, sex, and age. The proposed oxidation of tertiary amines to iminium ions by cytochrome P-450 may explain the isolation of various intramolecular and cyanide-trapped metabolites. N-oxides may represent a smaller percentage of the overall in vitro metabolism of tertiary amines due to the postmortem inactivation of MFAO. In addition N-oxide reducing enzymes present in vivo and in vitro may influence the extent of N-oxide formation. In general, definite conclusions about substrate requirements have been difficult to formulate because of the numerous biological and physical parameters affecting the outcome of metabolism. More singularly directed research on a single species of animal and a wide variety of substrates or vice versa would greatly increase our understanding of the potential metabolism of tertiary amine xenobiotics.