Metabolism of imipramine in vitro: synthesis and characterization of N-hydroxydesmethylimipramine.
The synthesis of N-hydroxydesmethylimipramine via the corresponding primary hydroxylamine and oxime is described. The N-oxygenated products are unstable to g.l.c. analysis without prior derivatization; the decomposition products are identified by g.l.c.-mass spectrometry. N-Hydroxydesmethylimipramine is shown to be a metabolite of imipramine and desmethylimipramine on incubation of either with fortified 9000 g liver homogenates of male New Zealand white rabbits. The metabolic product is characterized by mass spectrometry and n.m.r. Didesmethylimipramine is shown to undergo metabolic alpha-C-oxidation, to yield the carboxylic acid, 3-(10,11-dihydro-5H-dibenz[b, f]azepin-5-yl)propionic acid, but not N-oxidation. N-Hydroxydesmethylimipramine is metabolically reduced to desmethylimipramine and metabolized further to 10-hydroxydesmethylimipramine, 2-hydroxydesmethylimipramine and the carboxylic acid. The possible role of N-hydroxydesmethylimipramine and 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)propionic acid in the formation of iminodibenzyl is discussed.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003891:Desipramine / Q000031:analogs & derivatives / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007099:Imipramine / Q000031:analogs & derivatives / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D011817:Rabbits
C036691:didesipramine; C039939:N-hydroxydesipramine; D007099:Imipramine; D003891:Desipramine