Table 1.
Estimates of pKB from functional isolated tissue assays and selectivity ratios for dual ETA and ETB receptor antagonists in the absence or presence of endothelin‐1 clearance
| Receptor assay pKB | Ratio | ||||
|---|---|---|---|---|---|
| Endothelin antagonist | ETA Aortag , h | ETB Tracheag , i | ETB + Cj | ETA:ETB k | ETA:ETB + Cl |
| Bosentana | 7.3 | 5.9 | 4.9 | 25 | 250 |
| Ambrisentanb | 7.1 | 5.6 | 4.6 | 32 | 320 |
| Macitentanc | 7.6 | 5.9 | 4.9 | 50 | 500 |
| A‐182086d | 8.5m | 8.0m | 7.0 | 3 | 30 |
| Ro 46‐8443e | 5.7 | 7.1 | 6.1 | 0.04 | 0.4 |
| “Ideal”f | 8.5 | 8.5 | 7.5 | 1 | 10 |
a
Clozel et al.17
b
Bolli et al.33
c
Iglarz et al.34
d
Wessale et al.24
e
Breu et al.35
f
“Theoretical dualist.”
g
pKB from Schild plots.
h
Rat aorta (without endothelium) and agonist endothelin‐1.
i
Rat trachea (without epithelium) and agonist sarafotoxin S6c.
j
pKB for ETB receptors under the influence of endothelin‐1 clearance theoretically taken to be 10‐fold (ie, 1 log unit).
k
ETA to ETB selectivity ratio calculated as antilog (pKB ETA − pKB ETB).
l
ETA to ETB + C selectivity ratio calculated as antilog (pKB ETA − pKB ETB + C).
m
With endothelium.
Rabbit pulmonary artery (without endothelium).