CHLORPROMAZINE AND ITS METABOLITES ALTER POLYMERIZATION AND GELATION OF ACTIN

Hepatic hydroxylated metabolites of chlorpromazine (10-3M to 10-4M), 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 × 10 -4M) chlorpromazine inhibits actin polymerization. These dose-response relationships parallel the drug's hepatic toxicity in vivo and suggest that interactions between chlorpromazine or chlorpromazine metabolites and actin could be an underlying mechanism of cell injury.