METABOLISM OF TRIMIPRAMINE IN-VITRO BY HUMAN CYP2D6 ISOZYME

In vitro metabolism of the tricyclic antidepressant trimipramine using a commercial preparation of human CYP2D6 isozyme expressed in a human cell line is described. 2-Hydroxytrimipramine and a previously unrepo rted metabolite, 2,10- or 2,11-dihydroxy-trimipramine were isolated. T heir structures were determined by gas chromatography/ mass spectrosco py of underivatized and derivatized extracts. Acetylation of the new m etabolite resulted in dehydration at C-10 to give 10,11 -dehydro-2-ace toxytrimipramine, No N-dealkylation of trimipramine was observed. Prio r administration of quinidine produced a large reduction in the metabo lic oxidation of trimipramine with CYP2D6 while prior administration o f quinine had no effect. The use of this CYP2D6 isozyme preparation in vitro is of value in the identification of possible in vivo substrate s for the human CYP2D6 isozyme.