Macitentan-d is intended for use as an internal standard for the quantification of macitentan by GC- or LC-MS. Macitentan is a dual antagonist of the endothelin (ET) receptors type A and B (ICs = 0.5 and 391 nM in a radioligand binding assay using recombinant ET and ET, respectively). Macitentan inhibits intracellular Ca increases induced by the endothelin isoform ET-1 in human pulmonary arterial smooth muscle cells (HPASMCs; IC = 0.9 nM), contractions of isolated rat aortic rings (pA = 7.6 for ET), and sarafotoxin S6c-induced contractions of isolated rat tracheal rings (pA = 5.9 for ET). Macitentan increases plasma ET-1 concentrations in normotensive rats and decreases mean arterial blood pressure in DOCA-salt hypertensive rats (ED = 1 mg/kg). Oral administration (30 mg/kg per day) prevents development of pulmonary hypertension and right ventricle hypertrophy in a rat model of hypertension induced by monocrotaline . It also decreases the number of vascular and tubule-interstitial lesions and amount of glomerular damage in a rat model of diabetes induced by streptozotocin . Formulations containing macitentan have been used for the treatment of pulmonary arterial hypertension.