Affinity of Tezosentan for the ET receptors is assessed in different cells and tissues. Tezosentan inhibits the specific
125
I-labeled ET-1 binding to ETA receptors with an inhibitory potency (K
i
) of 0.3 nM on CHO cells and of 18 nM on membranes of baculovirus-infected insect cells. Similarly, Tezosentan inhibits the specific binding of
125
I-labeled ET-1, ET-3, or sarafotoxin S6c to ET
B
receptors with an inhibitory affinity of 10 to 21 nM. Tezosentan up to a concentration of 1 μM did not exhibit any binding inhibitory activity in 27 radioligand binding assays different from ET binding. On H1 central, 5-hydroxytryptamine2A, and vasopressin V1 receptors, Tezosentan (1 μM) induces a weak inhibition of less than 20%.