Chlorpromazine inhibits nitric oxide-mediated increase in intracellular cGMP in a mouse teratocarcinoma cell line

Chlorpromazine is a phenothiazine with a structure similar to that of methylene blue. Since methylene blue is a well known inhibitor of nitric oxide-induced cyclic GMP accumulation, we investigated whether chlorpromazine had the same effect. Cyclic GMP accumulation, induced in a mouse teratocarcinoma cell line (P19) by sodium nitroprusside (a nitric oxide releasing agent), was inhibited by both methylene blue (IC50 0.34 microM) and chlorpromazine (IC50 35 microM). Chlorpromazine's action was probably directed specifically at soluble guanylate cyclase, since the drug had no effect on ADP-ribosylation in rat hippocampus, another nitric oxide-affected, but cGMP-independent event.