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January 29, 1973

Mechanism of Estrogen-Imipramine Interaction

Author Affiliations

University of Pittsburgh

JAMA. 1973;223(5):560. doi:10.1001/jama.1973.03220050060032

To the Editor.—  This is a follow-up letter to the previous clinical reports by Prange (219:143, 1972) and Khurana (222:702, 1972), which did not include the mechanism of the estrogenimipramine interaction. This letter is intended to explain the biochemical basis of the said interaction.Imipramine is demethylated in the liver and other tissues to desmethylimipramine (DMP), which is further demethylated to desdimethylimipramine and later metabolized by hydroxylation and glucronide formation.1 In the rat, DMP is slowly metabolized and accumulates in different tissues of the body including the brain and retains the antidepressant activity.Steroids inhibit drug metabolism in vitro.2 Similarity exists in the properties of the enzyme system that metabolizes steroids in the liver and that which is responsible for the metabolism of many drugs and foreign compounds. A recent report,3 by measuring half-life of antipyrine and phenylbutazone in 36 women taking oral contraceptive steroids, has shown