title: Formation of the sulfone metabolite of didesmethylchlorpromazine in the rat in vivo and in vitro.
abstract: In peripheral tissues of male rats given 25 mg of didesmethylchlorpromazine [gamma-(2-chlorophenothiazinyl-10)-propylamine, Cl-PPA] per kg ip, high levels of the corresponding sulfoxide (Cl-PPA-SO) and the sulfone (Cl-PPA-SO2) were measured during the following 2-24 hr. Small quantities of these metabolites were excreted in bile, whereas 7-hydroxy-Cl-PPA could not be detected. By comparison of the areas under the tissue concentration-time curves with those measured after injection of Cl-PPA-SO2, it could be shown that at least 50% of the Cl-PPA dose was converted to the sulfone. Following administration of Cl-PPA-SO, the sulfone was present in tissues and in urine. An NADPH-dependent oxygenase catalyzing the conversion of Cl-PPA-SO to Cl-PPA-SO2 was localized in liver microsomes. Attempts to characterize the enzyme by means of induction and inhbition experiments did not lead to unequivocal conclusions concerning its nature.
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D013450:Sulfones / Q000378:metabolism; D013454:Sulfoxides / Q000378:metabolism
chemical_list: D013450:Sulfones; D013454:Sulfoxides; C022892:didemethylchlorpromazine; C022891:didemethylchlorpromazine sulfoxide; C022890:didemethylchlorpromazine sulfone; D002746:Chlorpromazine