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 oxideinduced 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 0.34µM) and chlorpromazine (IC₅₀ 35µM). 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.