Reduction of adriamycin cardiotoxicity by a new cardiotonic agent

Recently several non catecholamine, non glycoside cardiotonic drugs have been described. New compounds include amrinone, sulmazole, milrinone and pimobendan. In an attempt to alleviate anthracycline toxicity, we have previously reported that these compounds reduced the negative inotropic effect of adriamycin, 4-epiadriamycin and esorubicin in isolated guinea pig atria. The present study reports the effects of a new cardiotonic agent synthesized and studied by us: 2,3-Dihydro-6- (2,5-dimethoxyphenyl) imidazo [2,1-b]thiazole (VA-5), the most active of a series of 32 compounds with imidazo [2,1-b] thiazole and thiazoline moiety. Exposure for 60 to adriamycin (100 micrograms/ml) of electrically driven isolated guinea pig left atrium, in normodynamic or hypodynamic conditions, caused a depression of contractile force and of maximal rate of contractile force (df/dt). The negative effects of adriamycin are antagonized by VA-5 (100 micrograms/ml).