BQ-788 sodium salt is a potent and selective ETB receptor antagonist, with an IC50 of 1.2 nM for inhibiting ET-1 binding to ETB receptors in human Girrardi heart cells.
体内研究
In vivo, BQ-788 at a dose of 3 mg/kg/h intravenously, fully blocks ETB receptor-mediated depressor responses to ET-1 or sarafotoxin6c in conscious rats, significantly increases plasma ET-1 levels—indicating effective ETB receptor blockade—and raises blood pressure by approximately 20 mm Hg in Dahl salt-sensitive hypertensive rats. It also counters ET-1-induced bronchoconstriction, tumor growth, and lipopolysaccharide-induced organ failure[1].
Furthermore, a 3 mg/kg dose of BQ-788 significantly modifies the ET-1 dose-response curve, highlighting the role of ETB dilator receptors[2].
In mice, 30 nmol of BQ-788 administered intraplantarly reduces mechanical and thermal hyperalgesia, oedema, myeloperoxidase activity, and overt pain-like behaviors. Intraplantar administration of either clazosentan or BQ-788 also decreases superoxide anion production and lipid peroxidation both in the spinal cord and peripherally[3].
体外研究
BQ-788 sodium salt competitively inhibits 125I-ET-1 binding to ETB receptors in these cells with similar potency but shows significantly less affinity for ETA receptors in SK-N-MC human neuroblastoma cells, with an IC50 of 1300 nM. BQ-788 does not exhibit agonistic activity up to 10 μM and competitively blocks vasoconstriction triggered by an ETB-selective agonist. Additionally, BQ-788 impedes several ET-1-mediated bioactivities, including bronchoconstriction, cell proliferation, and ET-1 clearance[1].
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