Palosuran is an antagonist of the urotensin II receptor (UTR; IC50s = 3.6 and 1,475 nM for CHO cell membranes expressing human and rat recombinant receptors, respectively).1 It inhibits contraction of isolated rat aortic rings induced by urotensin II in a concentration-dependent manner. Palosuran (300 mg/kg twice per day) reduces plasma endothelin-1 , urotensin II, and TGF-β1 levels, as well as the main pulmonary arterial pressure and right ventricular hypertrophy index in a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline .2 Palosuran (300 mg/kg per day) reduces serum glucose, cholesterol, and triglyceride levels and increases survival in a rat model of diabetes induced by streptozotocin .3 It also decreases albuminuria and global kidney lesion scores in STZ-induced diabetic rats.
1.Clozel, M., Binkert, C., Birker-Robaczewska, M., et al.Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): First demonstration of a pathophysiological role of the urotensin systemJ. Pharmacol. Exp. Ther.311(1)204-212(2004) 2.Onat, A.M., Pehlivan, Y., Turkbeyler, I.H., et al.Urotensin inhibition with palosuran could be a promising alternative in pulmonary arterial hypertensionInflammation36(2)405-412(2013) 3.Clozel, M., Hess, P., Qiu, C., et al.The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic ratsJ. Pharmacol. Exp. Ther.316(3)1115-1121(2006)