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 nitr ic oxide-induced cyclic GMP accumulation, we investigated whether chlo rpromazine had the same effect. Cyclic GMP accumulation, induced in a mouse teratocarcinoma cell line (P19) by sodium nitroprusside (a nitri c oxide releasing agent), was inhibited by both methylene blue (IC50 0 .34 mu M) and chlorpromazine (IC50 35 mu M). Chlorpromazine's action w as 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.