Chlorpromazine inhibits human natural killer cell activity and antibody-dependent cell-mediated cytotoxicity.

The phenothiazine antipsychotic drug chlorpromazine, a potent calmodulin antagonist, inhibited human natural killer cell-mediated cytotoxicity in a dose-dependent manner. This inhibition of natural killer cell activity was not due to interference with conjugate formation, nor was it due to toxicity to the natural killer cells or nonspecific alteration of the target cells. Chlorpromazine also suppressed antibody-dependent cell-mediated cytotoxicity in a dose-dependent fashion, suggesting that the two activities share a calmodulin-dependent step. Finally, it was not possible to overcome chlorpromazine-mediated inhibition of natural killer cell activity by first treating the cells with interleukin-2 or Beta-interferon.