Abstract
Summary
Chlorpromazine (CPZ) and several of its metabolites were tested for in vitro cytotoxicity, as measured by the efflux of aspartate aminotransferase to the surrounding medium, toward isolated rat hepa-tocytes. Exposure of liver cells to CPZ, at a concentration of 9 × 10-5 M, led to enzyme leakage. The demethylated metabolites, mono- and didesmethyl-CPZ, were three and six times, respectively, more potent than CPZ. Hydroxylation of the tricyclic ring at the 7 or 8 position gives rise to compounds that were slightly less active than the parent compound, while oxidation of the sulfur atom resulted in inactive analogs. The presence of calcium in the medium had no apparent effect on the response of the hepatocytes to CPZ.
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