Endothelin Receptor Antagonists

Endothelin Receptor Antagonists

1. Definition & scope

• Endothelin receptor antagonists (ERAs) are orally active, non-peptide, small-molecule competitive antagonists of endothelin receptors that block the vasoconstrictor, mitogenic and profibrotic actions of endothelin-1 (ET-1); the class comprises bosentan, macitentan and ambrisentan, and is a first-line oral pharmacotherapy for pulmonary arterial hypertension (PAH) (G&G 14e Ch.35, pp.701–703; KDT 8e Ch.37, pp.546–547).
• ETs are a trio of closely related 21–amino-acid peptides (ET-1, ET-2, ET-3), each the product of a different gene, with potent vasoconstrictor activity; ET-1 is the predominant and functionally most relevant isoform, generated chiefly by vascular endothelial cells (KDT 8e Ch.37, p.544; G&G 14e Ch.35, p.701).
• Rationale for the class: in PAH there is a pathological imbalance between vasoconstrictor/mitogenic mediators (ET-1, thromboxane A₂, 5-HT) and vasodilator/antiproliferative mediators (NO, prostacyclin/PGI₂); antagonising ET-1 helps restore that balance, reducing vasoconstriction, vascular remodeling and in situ thrombosis (G&G 14e Ch.35, pp.696–697, Fig.35–7; KDT 8e Ch.37, p.546).
• Scope note: this account covers the endothelin system and its receptor antagonists; the parallel NO/cGMP (sildenafil, riociguat) and prostacyclin (epoprostenol, treprostinil, iloprost, selexipag) classes are described only as comparators/combination partners, not as primary content (G&G 14e Ch.35, pp.698–701).