Anthracyclines cardiotoxicity: antagonism by sulmazole, a new cardiotonic agent.

In attempts to alleviate or prevent anthracyclines toxicity, we have recently reported that amrinone markedly reduced the negative inotropic effect of adriamycin in isolated guinea pig atria, in normodynamic or hypodynamic conditions (medium with reduced calcium content). Previous experiments on isolated guinea pig atria showed that the negative inotropic action of anthracyclic compounds was enhanced in hypodynamic conditions. The present study reports the effects of 4-epiadriamycin on spontaneously beating guinea pig atria, in normo- or hypodynamic conditions. 4-Epiadriamycin (100 micrograms/ml) exerts a negative inotropic and chronotropic effect which matches that of adriamycin. The negative effects of the two antitumoral drugs are antagonized by sulmazole, a benzimidazole derivative with cardiotonic activity. In contrast to cardiac glycosides, the new compounds (amrinone, sulmazole, and derivatives) could be experimented in an attempt to antagonize the toxicity of anthracyclic compounds.