title: Different regiospecificity in the hydroxylation of the antidepressant desmethylimipramine between rat brain and liver.
abstract: Incubation of the tricyclic antidepressant desmethylimpramine (DMI) with rat liver or brain microsomes in the presence of NADPH or t-butyl-hydroperoxide (TBH) revealed different regiospecificities in the hydroxylation reactions between the tissues. In brain preparations 10-OH-DMI was formed in reactions supported by NADPH or TBH, whereas in the latter case also an unidentified metabolite could be detected. Inclusion of exogenous NADPH-cytochrome P450 reductase in the brain preparations caused a 10-fold higher rate of 10-hydroxylation but no 2-OH-DMI could be detected. By contrast, liver microsomal preparations in the presence of NADPH catalyzed formation of both 2- and 10-OH-DMI, whereas only 10-OH-DMI was formed in TBH-supported reactions. The results indicate that antidepressant drugs can be metabolized in brain with different stereospecificity as compared to liver.
authors: Department of Drug Metabolism, Astra Research Centre, Södertälje, Sweden.
authors: T
authors: T
authors: Hansson
authors: C
authors: C
authors: von Bahr
authors: M
authors: M
authors: Marklund
authors: J O
authors: JO
authors: Svensson
authors: M
authors: M
authors: Ingelman-Sundberg
authors: J
authors: J
authors: Lundström
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003891:Desipramine / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020122:tert-Butylhydroperoxide
chemical_list: D010545:Peroxides; D009249:NADP; D020122:tert-Butylhydroperoxide; D003891:Desipramine