Ambrisentan-d3 is intended for use as an internal standard for the quantification of ambrisentan by GC- or LC-MS. Ambrisentan is a nonpeptide endothelin A (ETA) receptor antagonist (IC50s = 0.251, 0.316, 0.398, 251, and 630 nM for rat preparations of heart, bladder, kidney, lung, and cerebral cortex, respectively).1 It inhibits contraction of isolated rabbit aortic rings induced by endothelin-1 by 43.23% when used at a concentration of 1 µM.2 Ambrisentan inhibits ET-1-induced contraction of human pulmonary and radial arteries in vitro (Kd = 0.042 and 0.11 μM, respectively).3 In a rat model of neonatal hyperoxic lung injury, ambrisentan (20 mg/kg per day, s.c.) reduces pulmonary arterial hypertension (PAH) as well as decreases PAH-induced right ventricular hypertrophy (RVH) and peak RV pressure.4 Formulations containing ambrisentan have been used in the treatment of PAH.
1.Yokoyama, Y., Osano, A., Hyashi, H., et al.Endothelin-1 receptors in rat tissues: Characterization by bosentan, ambrisentan and CI-1020Biol. Pharm. Bull.37(3)461-465(2014) 2.Xia, J., Song, J., Zhen, L., et al.Synthesis and in vitro evaluation of ambrisentan analogues as potential endothelin receptor antagonistsBioorg. Med. Chem. Lett.21(13)3894-3897(2011) 3.Angus, J.A., Soeding, P.F., Hughes, R.J.A., et al.Functional estimation of endothelin-1 receptor antagonism by bosentan, macitentan and ambrisentan in human pulmonary and radial arteries in vitroEur. J. Pharmacol.804111-116(2017) 4.Wagenaar, G.T., Laghmani, e.H., de Visser, Y.P., et al.Ambrisentan reduces pulmonary arterial hypertension but does not stimulate alveolar and vascular development in neonatal rats with hyperoxic lung injuryAm. J. Physiol. Lung Cell Mol. Physiol.304(4)L264-L275(2013)