Biphasic effects of chlorpromazine on cell viability in a neuroblastoma cell line

Although chlorpromazine was shown to greatly inhibit a Ca²⁺-mediated cell death at favorable concentrations (10^-6 ∼ 10^-5 M), it caused a drastic decrease in cell viability at higher concentrations (10^-4 ∼ 10^-3 M) in a human neuroblastoma cell line. The toxic effect of chlorpromazine also occurred in Ca²⁺-free medium and was not parallel to the amount of thiobarbituric acid-reactive substances produced. These results indicate that chlorpromazine has biphasic effects on cell viability according to the concentrations added, i.e. a protective effect against cell damage caused by Ca²⁺, and a direct toxic effect independent of extracellular Ca²⁺ or of lipid peroxidation.