title: QSAR study on species differences in microsomal N-oxygenation of N,N-dimethylalkylamines.
abstract: The metabolic N-oxygenation of nine long chain N,N-dimethylalkylamines and tri-n-butylamine has been studied using hepatic microsomal homogenates from mice, dogs and guinea-pigs. The relative oxidizability of amines (ROA) was correlated with structure, lipophilicity and nucleophilicity parameters of substrates and corresponding amine oxides formed in this biological reaction. The highest conversion of amines to N-oxides was found with male guinea-pig, followed by dog (male, female) and the lowest amount of amine oxides has been produced with male mice microsomal homogenates. The analyses were carried out by GLC and the results quantified using QSAR methodology. ROA is parabolically dependent upon structure and physicochemical properties of the substrates and products which was proved by the high statistical significance of the regression equations. The biological N-oxygenation of these amines is controlled by lipophilicity, stereochemistry and electronic effects.
authors.affiliation: Chelsea Department of Pharmacy, King's College London, University of London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Devínsky
authors.forename: J W
authors.initials: JW
authors.lastname: Gorrod
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004123:Dimethylamines / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D004123:Dimethylamines