Modifications of sphingomyelin and phosphatidylcholine metabolism by tricyclic antidepressants and phenothiazines.
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.
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*
D000929:Antidepressive Agents, Tricyclic; D010640:Phenothiazines; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D007099:Imipramine; D003891:Desipramine; D002746:Chlorpromazine