Chlorpromazine and its metabolites alter polymerization and gelation of actin

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Science  21 Dec 1979:
Vol. 206, Issue 4425, pp. 1404-1406
DOI: 10.1126/science.574316


Hepatic hydroxylated metabolites of chlorpromazine (10(-5)M to 10(-4)M), a frequently used phenothiazine tranquilizer, produce solid gel formation with filamentous actin, but the less toxic chlorpromazine sulfoxide metabolite does not. At higher concentrations (5 x 10(-4)M) chlorpromazine inhibits actin polymerization. These dose-response relationships parallel the drug's hepatic toxicity in vivo and suggest that interactions between chloropromazine or chlorpromazine metabolites and actin could be an underlying mechanism of cell injury.