BQ-788 sodium salt is a potent and selective antagonist of ETB receptor [ETB receptors] with an IC50 of 1.2 nM in human Girrardi heart cells.

ETB:1.2 nM

BQ-788 potently and competitively inhibits 125I-labeled ET-1 binding to ETB receptors in human Girrardi heart cells (hGH) with an IC50 of 1.2 nM, while poorly inhibiting ETA receptor binding in human neuro-blastoma cell line SK-N-MC cells (IC50, 1300 nM). It inhibits ET-1 bioactivities, including bronchoconstriction, cell proliferation, and clearance of perfused ET-1[1], and shows no agonistic activity up to 10 μM. Additionally, BQ-788 competitively inhibits vasoconstriction induced by an ETB-selective agonist (pA2, 8.4).

Administered intravenously at a dosage of 3 mg/kg/h, BQ-788 effectively blocks the ETB receptor-mediated depressor responses induced by pharmacological levels of ET-1 or sarafotoxin6c (0.5 nmol/kg) in conscious rats, without affecting pressor responses. In Dahl salt-sensitive hypertensive rats, this dosage of BQ-788 results in a significant increase in blood pressure, approximately 20 mm Hg. Moreover, BQ-788 is noted to inhibit ET-1-induced bronchoconstriction, tumor proliferation, and lipopolysaccharide-triggered organ failure. It notably shifts the ET-1 dose-response curve eightfold to the left, highlighting a substantial role of ETB dilator receptors. Additionally, BQ-788 significantly raises plasma ET-1 levels, indicating its potential as an ETB receptor blocker in vivo. In mice, intraplantar administration of 30 nmol BQ-788 reduces mechanical and thermal hyperalgesia, oedema, and myeloperoxidase activity by significant margins, alongside diminishing overt pain-like behaviors. Likewise, intraplantar interventions with either clazosentan or BQ-788 lower superoxide anion production and lipid peroxidation in both spinal and peripheral contexts.