Effect of milrinone analogues on intracellular calcium increase in single living H9C2 cardiac cells

The synthesis of milrinone analogues where the 4-pyridyl moiety was replaced by an ester or amide
group is reported. Only amide derivatives are able to support intracellular calcium influx following
chemical depolarization with 60 mM KCl in a percentage varying from 20 to 45% of differentiated H9C2
cardiomyocytes. Those cells were differentiated after chronic exposure to 10 nM retinoic acid which
induces the expression of voltage-gated calcium channels. Analogues of milrinone containing an ester
function did not show significant activity.