Sitaxsentan is a selective endothelin-A (ETA) receptor antagonist launched for the treatment of patients with pulmonary arterial hypertension (PAH), to
improve exercise capacity. It is the second ET receptor antagonist to be marketed
for this indication behind bosentan. PAH encompasses a heterogeneous group of
disorders characterized by inappropriate overactivation of the endothelin system
and is characterized by a progressive increase in pulmonary vascular resistance
resulting from vascular remodeling, vasoconstriction, and cellular proliferation.
Endothelin-1 (ET-1), a potent vasoconstrictor and smooth muscle mitogen, is a
key contributor to the acceleration of the disease, and its effects are mediated
through activation of ETA and ETB receptors. ETA receptors are found primarily
on smooth muscle cells and, when activated, induce vasoconstriction and cellular
proliferation. ETB receptors are expressed in both pulmonary vascular endothelial
cells and smooth muscle cells, and their activation is associated with the
renal and pulmonary clearance of ET.
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