Iloprost-d4 is intended for use as an internal standard for the quantification of iloprost by GC- or LC-MS. Iloprost is an agonist of the IP receptor and the prostaglandin E2 (PGE2) receptor subtype EP1 and a derivative of PGI2.[1],[2] It selectively binds to IP and EP1 receptors (Ki = 11 nM for both) over EP2, EP4, DP, FP, and TP receptors (Kis = 1,870, 284, 1,035, 619, and 6,487 nM, respectively) but also binds to the EP3 receptor (Ki = 56 nM).[1] Iloprost increases cAMP levels in HEK293 cells expressing IP or EP3 receptors (EC50s = 0.37 and 27.5 nM, respectively) and increases calcium levels in HEK293 cells expressing the EP1 receptor (EC50 = 0.3 nM).[2] It inhibits ADP-, thrombin-, and collagen-induced platelet aggregation in isolated human platelet-rich plasma (IC50s = 1.07, 0.71, and 0.24 nM, respectively).[3] Iloprost (100 ng/kg per minute) increases the time to occlusive coronary artery thrombosis in a porcine model of electrically induced coronary artery thrombosis.[4] Aerosolized administration of iloprost (130-1,300 ng/kg per minute) reduces right ventricular systolic pressure and reverses vascular remodeling in rats in a model of chronic pulmonary hypertension induced by the alkaloid monocrotaine .[5] Formulations containing iloprost have been used in the treatment of pulmonary arterial hypertension and severe frostbite.
References:
[1].Abramovitz, M., Adam, M., Boie, Y., et al.The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogsBiochim. Biophys. Acta1483(2)285-293(2000).
[2].Whittle, B.J., Silverstein, A.M., Mottola, D.M., et al.Binding and activity of the prostacyclin receptor (IP) agonists, treprostinil and iloprost, at human prostanoid receptors: Treprostinil is a potent DP1 and EP2 agonistBiochem. Pharmacol.84(1)68-75(2012).
[3].Schrör, K., Darius, H., Matzky, R., et al.The antiplatelet and cardiovascular actions of a new carbacyclin derivative (ZK36374) — equipotent to PGI2 in vitroNaunyn Schmiedebergs Arch. Pharmacol.316(3)252-255(1981).
[4].van der Giessen, W.J., Mooi, W.J., Rutteman, A.M., et al.The effect of the stable prostacyclin analogue ZK 36374 on experimental coronary thrombosis in the pigThromb. Res.36(1)45-51(1984).
[5].Schermuly, R.T., Yilmaz, H., Ghofrani, H.A., et al.Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertensionAm. J. Respir. Crit. Care Med.172(3)358-363(2005).