Darusentan is an endothelin type A (ETA) receptor antagonist (Ki = 13 nM in rat aortic vascular smooth muscle cells).1 It inhibits contractions induced by human endothelin-1 in isolated rat aortic rings and mesenteric microvessels with pA2 values of 8.1 and 7.97, respectively. Darusentan (50 mg/kg) decreases systolic blood pressure in DOCA-salt hypertensive rats, as well as reduces mean arterial pressure (MAP) and left ventricular developed pressure (LVDP) in normotensive pigs when administered at doses of 1 and 5 mg/kg.2,3 It reduces myocardial infarct size as a percentage of the area at risk in a porcine model of ischemia-reperfusion injury induced by ligation of the left anterior descending (LAD) coronary artery.3
1.Liang, F., Glascock, C.B., Schafer, D.L., et al.Darusentan is a potent inhibitor of endothelin signaling and function in both large and small arteriesCan. J. Physiol. Pharmacol.88(8)840-849(2010) 2.Schiffrin, E.L., Turgeon, A., and Deng, L.Y.Effect of chronic ETA-selective endothelin receptor antagonism on blood pressure in experimental and genetic hypertension in ratsBr. J. Pharmacol.121(5)935-940(1997) 3.Gonon, A.T., Wang, Q.D., Shimizu, M., et al.The novel non-peptide selective endothelin A receptor antagonist LU 135 252 protects against myocardial ischaemic and reperfusion injury in the pigActa Physiol. Scand.163(2)131-137(1998)