Depletion of cellular beta-hexosaminidase by imipramine is prevented by dexamethasone; implications for treating psychotic hexosaminidase-A deficient patients.
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.
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005733:Gangliosidoses / Q000188:drug therapy; D054818:Hexosaminidase A; D006801:Humans; D007099:Imipramine / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency / Q000378:metabolism*
D003907:Dexamethasone; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases; D007099:Imipramine