Palosuran hydrochloride (ACT-058362 hydrochloride) is a potent, selective, and orally active antagonist of urotensin II receptor, with an IC50 of 3.6 nM for CHO cell membranes expressing human recombinant receptors. Palosuran hydrochloride can improves pancreatic and renal function in diabetic rats[1][2].

Palosuran (8 h) inhibits 125I-U-II binding to human UT receptor, with IC50s of 46.2 nM on TE 671 cells and 86 nM on recombinant CHO cells[1].Palosuran inhibits Ca2+ mobilization in response to human U-II in CHO cells expressing human and rat UT receptor with IC50s of 17 and >10000 nM, respectively[1].Palosuran (0.12-10000 nM; 20 min) inhibits human U-II induced MAPK phosphorylation in a dose-dependent manner in recombinant CHO cells, with an IC50 of 150 nM[1].

ACT-058362 (10 mg/kg/h; i.v.) fully prevents the decrease in renal blood flow after ischemia in rats without decreasing blood pressure[1].Palosuran (300 mg/kg/d; p.o. for 16 weeks) improves the survival, increases insulin, and slows the increase in glycemia, glycosylated hemoglobin, and serum lipids in streptozotocin-induced diabetic rats[2]. Animal Model: Male Wistar rats with renal ischemia and reperfusion[1]

[1]. Clozel 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 System. J Pharmacol Exp Ther. 2004 Oct;311(1):204-12. [2]. Clozel M, et, al. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21.