Depletion of cellular beta-hexosaminidase by imipramine is prevented by dexamethasone; implications for treating psychotic hexosaminidase-A deficient patients

Abstract

Normal human skin fibroblasts secrete most of their hexosaminidase (Hex) into the medium upon incubation with 10(-4) imipramine, while preincubation with 2.5 X 10(-9) M dexamethasone prevents this effect. These results support the hypotheses that 1) treatment of psychotic Hex A deficient patients with amphiphilic antidepressants (such as imipramine) aggravates the patients' disease through depletion of their residual cellular Hex A, and 2) concomitant medication with dexamethasone may mitigate this drug-induced deleterious effect.