title: Modifications of sphingomyelin and phosphatidylcholine metabolism by tricyclic antidepressants and phenothiazines.
abstract: Phenothiazines and tricyclic antidepressants, when added to culture medium, gave rise in several types of cells (C6 rat glioma cells and human fibroblasts), to a decrease in lysosomal sphingomyelinase activity. The effect of chlorpromazine and desipramine was dose dependent, and was observed after 3 hours of incubation with the drugs at concentrations ranging between 1 and 10 microM. In C6 glioma cell cultures, the decrease in sphingomyelinase activity was related to the clinical effectiveness of phenothiazines, tricyclic antidepressants and derivatives. Incorporation of (choline-14C) sphingomyelin showed that the metabolic pathway implying the synthesis of phosphatidylcholine from the hydrolysis of sphingomyelin and/or transfer of phosphorylcholine to phosphatidylcholine was also partially reduced.
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002460:Cell Line; D002746:Chlorpromazine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D007700:Kinetics; D008247:Lysosomes / Q000201:enzymology; D009542:Niemann-Pick Diseases / Q000378:metabolism; D010640:Phenothiazines / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D010640:Phenothiazines; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D007099:Imipramine; D003891:Desipramine; D002746:Chlorpromazine