Cariporide

Cariporide (HOE642) is a potent, selective sodium-hydrogen exchange subtype 1 (NHE1) inhibitor with IC50 of 50 nM, little to no activity against NHE3 and NHE2 (IC50=3 and 10 uM) ; inhibits the amiloride sensitive sodium influx in rabbit erythrocytes, reduces the swelling of human platelets induced by intracellular acidification, and delays pH recovery in rat cardiomyocytes; reduces and prevents ventricular premature beats, ventricular tachycardia, and ventricular fibrillation after oral treatment in vivo, shows cardioprotective and antiarrhythmic effects in ischaemic and reperfused hearts.Heart Arrhythmia Phase 2 Discontinued (In Vitro) :Cariporide significantly suppresses markers of cell death, such as TUNEL positivity and caspase-3 cleavage, at 8 or 16 hours. Cariporide remarkably suppresses cytosolic Na+ and Ca2+ accumulation. Cariporide prevents mitochondrial membrane potential loss induced by H2+O2+. Cariporide (HOE-642) ameliorates myocardial ischemia/reperfusion injury, by the well-established reduction of cytosolic Ca2+ in cardiac myocytes through inhibition of Na+/H+ exchange. Cariporide (HOE-642), has inhibitory effects on the degranulation of human platelets, the formation of platelet–leukocyte-aggregates, and the activation of the GPIIb/IIIa receptor (PAC-1) . (In Vivo) :Intravenous administration of cariporide significantly decreases brain Na+ uptake and reduces cerebral edema, brain swelling, and infarct volume.