Caldaret is an intracellular Ca2+ handling modulator that acts through reverse mode Na+/Ca2+ exchanger inhibition.

Caldaret resume Ca2+-ATPase activity of the sarcoplasmic reticulum isolated from the myocardium acutely exposed to ischemia and reperfusion in vitro [2].

Caldaret (MCC-135) has beneficial effects in heart failure. In diabetic rats, Caldaret decreases TR80 significantly without a significant effect on developed tension (DT). Caldaret has minimal effects on SR Ca2+ uptake in normal rats, which is observed as increased SR Ca2+ uptake at uptake time of 20 and 30 s at the highest concentration of 10 μM. In diabetic rats, Caldaret increases SR Ca2+ uptake all over the range of uptake time. Both the initial rate of SR Ca2+ uptake and the amount of Ca2+ accumulated in the SR with longer uptake time are increased by Caldaret [2]. Caldaret limits the infarct size of the reperfused canine heart. The amelioration of intracellular Ca2+ handling dysfunction achieved by Caldaret leads to cardioprotective effects against reperfusion injury following prolonged ischemia [1].