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

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Abstract

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.

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Abbreviations

SNP:

sodium nitroprusside

NO:

nitric oxide

cGMP:

cyclic GMP

cAMP:

cyclic AMP

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Authors and Affiliations

  1. Istituto di Ricerche Farmacologiche “Mario Negri”, Via Eritrea, 62, 1-20157, Milano, Italy

    M. Fratelli, M. Zinetti, G. Galli & P. Ghezzi

  2. Center for Pharmaceutical Chemistry, Havana, Cuba

    R. Delgado

  3. Institut de Recherches Servier, Suresnes, France

    Y. Rolland

Authors
  1. M. Fratelli
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  2. R. Delgado
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  3. M. Zinetti
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  4. G. Galli
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  5. Y. Rolland
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  6. P. Ghezzi
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Fratelli, M., Delgado, R., Zinetti, M. et al. Chlorpromazine inhibits nitric oxide-mediated increase in intracellular cGMP in a mouse teratocarcinoma cell line. Inflamm Res 44, 287–290 (1995). https://doi.org/10.1007/BF02032570

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  • DOI: https://doi.org/10.1007/BF02032570

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