The Na+/H+ exchange inhibitor cariporide: preclinical profile and approachto clinical development

NHE-1 has been identified as an ion transport system which plays a crucial role in the pathophysiology of myocardial ischaemia/reperfusion. By inhibit ion of the NHE, intracellular Na+ and Ca2+ overload can be reduced and the progression of the myocardium from ischaemia to necrosis can be delayed. Th e specific and potent NHE-1 inhibitor cariporide has been characterized in erythrocytes, platelets fibroblasts and myocardial cells from different spe cies, including humans. Protective effects in ischaemia/reperfusion have be en demonstrated in numerous experiments in isolated cells, isolated hearts and in in vivo models in different species. The NHE inhibitor was protectiv e against all kinds of ischaemia/reperfusion injury of the heart such as ar rhythmias, contracture, stunning and necrosis. The protective effects of th e compound were most pronounced when it was given before the ischaemic even t and less pronounced when it was given on reperfusion only. According to t his profile, cariporide was tested in a patient population at high risk of an ischaemic cardiac event, in a large clinical phase II/III trial, which i s currently under evaluation.