Pulmonary arterial hypertension receptor antagonist

Bosentan Nonselective antagonist of endothelin ETA and ETB receptors Vasodilation Pulmonary arterial hypertension... 

Dupuis J, Hoeper MM Endothelin receptor antagonists in pulmonary arterial hypertension. Eur Respir J 2008 31 407. [PMID 18238950]... 

Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarhn J. Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension open-label pilot study. Chest 2002 121(6) 1860-8. 

Badesch DB, Bodin F, Channick RN, Frost A, Rainisio M, Robbins IM, Roux S, Rubin LJ, Simonneau G, Sitbon O, Tapson VF. Complete results of the first randomized, placebo-controlled study of bosentan, a dual endothelin receptor antagonist, in pulmonary arterial hypertension. Curr Ther Res Clin Exp 2002 63 227M6. 

Indications Pulmonary arterial hypertension Category Endothelin receptor antagonist Vasodilator Half-life 15 Hours... 

Ahmadi-Simab K, Lamprecht P, Hellmisch B, Gross WL. Treatment of pulmonary arterial hypertension (PAH) with oral endothelin-receptor antagonist bosentan in systemic sclerosis BREATHE-1 trial and clinical experience. Z Rheumatol 2004 63(6) 495-7. [Article in German]... 

Barst RJ, Langleben D, Badesch D, et al STRIDE-2 Study Group. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006 47(10) 2049-56. 

Bosentan is an endothelin receptor antagonist. It antagonized endothelin (ET) receptor by binding to ET and ETg receptors in the endothelium and vascular smooth muscle. Bosentan is indicated in treatment of pulmonary arterial hypertension in patients with WHO class III and IV symptoms, to improve exercise ability, and decrease the rate of clinical worsening. 

Ambrisentan is a powerful receptor antagonist that is clinically used for the treatment of pulmonary arterial hypertension. Very recently, Shi s group has applied his methodology to the epoxidation of 3,3-diphenylacrylate 69, which was transformed in four steps into (-l-)-ambrisentan in 53% overall yield and can be carried out in large scale (120g) (Scheme 12.15) [106]. 

Secondary causes of pulmonary arterial hypertension (PAH), including appetite suppressant drugs associated with PAH, have been reviewed [97 j. Newer trends in the treatment of PAH, especially the status of prostacyclin analogues and endothelin-1 receptor antagonists, have been addressed. 

Bosentan The pharmacokinetic interaction of sildenafil and the dual endotheUn receptor antagonist bosentan, both of which are marketed for the treatment of pulmonary arterial hypertension, has been studied in 55 healthy men [31 ]. Bosentan reduced the Cnmx and AUCx of sildenafil, and sildenafil increased the corresponding values of bosentan. The clinical implications for combined therapy are not known. 

Liver The availability of ambrisentan in patients with pulmonary artery hypertension who have previously discontinued other endothelin receptor antagonists because of liver function abnormalities provides an important option for patients who have had adverse reactions to bosentan or sitaxsentan [76 ]. Ambrisentan is a... 

The endothelins interact with two endothelin receptors, ETa and ETb. Endothelins are highly potent vasoconstrictors and endothelin antagonists have the potential to be used clinically to treat pulmonary arterial hypertension (PAH), congestive heart failure, stroke, kidney failure, asthma, pain, and cancer. The small molecule bosentan (Tracleer) interacts with both ETa and ETb receptors and was the first endothelin antagonist to be used clinically for the treatment of PAH. Additional compounds are in clinical development or have reached the market. ... 

Trials of the effects of endothelin receptor antagonists in patients with heart failure, coronary artery disease, arterial hjtpertension, and pulmonary hjtpertension have been reviewed (6), as have their uses in treating cancers (7) and cerebral vasospasm (8), and their potential uses in atherosclerosis, re-stenosis, myocarditis, shock, and portal hypertension (9)... 

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