An in vitro study on the interaction between ethanol and imipramine at high concentrations using human liver microsomes

Imipramine is a tricyclic antidepressant that iswidely used for the treatment of major depression. Thereis a possibility that toxic interactions occur followingcombined use of imipramine and intake of alcohol. Inthis study, we investigated the in vitro interactionbetween ethanol and imipramine at high concentrationsby observing a mixed-function oxidation reaction usinghuman liver microsomes. Imipramine and its three mainmetabolites (desipramine; 2-hydroxyimipramine, 2-OHI;2-hydroxydesipramine, 2-OHD) were measured by highperformanceliquid chromatography with ultravioletdetection. The production of 2-OHD, the main metaboliteof imipramine, was signifi cantly inhibited, by 15%–50% (P < 0.05), by ethanol, but that of desipramine or2-OHI was not. These results suggest that enhanced toxicityis attained by simultaneous use of ethanol and highdose of imipramine in the human body