Bosentan hydrate (Ro 47-0203) is a synthetic nonpeptide compound that acts as an antagonist of endothelin A (ET-A) and endothelin B (ET-B) receptors. Bosentan hydrate is obtained by structural optimization of Ro 46-2005, a less potent ET-A/ET-B antagonist that is orally bioavailable and active in vivo. Bosentan hydrate competitively inhibits the specific binding of radioligand endothelin-1 to ET-A receptors in human smooth muscle cells with K_i value of 4.7 nM, and to ET-B receptors in human placenta with a K_i of 95 nM¹. Bosentan may be a useful drug in the management of clinical disorders associated with vasoconstriction^1,2.

ET-A receptors are predominantly detected in peripheral tissues, especially in vascular smooth muscle tissues where they mediate vasoconstriction. They are also expressed in several regions of the brain. ET-B receptors play an important role in regulating renal function and blood pressure and are expressed in sensory nerves. They are mainly present in medium- and large-sized cell bodies of human trigeminal ganglia. The ET-A receptor has high affinity for endothelin-1 and endothelin-2 and relatively low affinity for endothelin-3, while the ET-B receptor has high affinity for all endothelin isopeptides^3,4_.