Effect of iprindole on the metabolism of trimipramine in the rat.

ABSTRACT

Major metabolites of trimipramine in young male Sprague-Dawley rats are the result of alicyclic and aromatic ring oxidation. The four major urinary metabolites have been identified as 10-oxotrimipramine, 2-hydroxytrimipramine, 2-hydroxynortrimipramine, and 2-hydroxy-10-oxotrimipramine. When iprindole was administered to rats prior to trimipramine, the effect on trimipramine metabolism was profound. The formation of both 10-oxo metabolites was virtually completely inhibited; the production of 2-hydroxytrimipramine was significantly reduced while the metabolic formation of 2-hydroxynortrimipramine was increased. It is apparent from these preliminary results that metabolic alicyclic and aromatic hydroxylations are catalyzed by different cytochrome P450 isozymes and more than one P450 isozyme is involved in the aromatic ring oxidation of trimipramine and nortrimipramine.