Chlorpromazine and its metabolites alter polymerization and gelation of actin.
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.
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005782:Gels; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits; D014783:Viscosity
D000199:Actins; D005782:Gels; D002746:Chlorpromazine