Uses
Antagonist
(endothelin receptor).
Definition
ChEBI: Bosentan hydrate is a hydrate. It contains a bosentan.
Brand name
Tracleer (Actelion).
Biological Activity
a sulfonamide-derived, competitive and specific endothelin receptor antagonist with a relatively higher affinity to the endothelin a receptor than endothelin b receptor. by competitively binding to endothelin a and endothelin b receptors in the endothelium and vascular smooth muscle, bosentan offset the effect of endothelin which is an extremely potent endogenous vasoconstrictor and broncho-constrictor. in addition, bosentan decreases both pulmonary and systemic vascular resistance and is particularly applied in the treatment of pulmonary arterial hypertension. [1]
Biochem/physiol Actions
Bosentan is an endothelin receptor antagonist. Endothelin is a potent vasoconstrictor, making antagonists of clinical interest for the treatment of conditions associated with vasospasm, such as subarachnoid hemorrhage (SAH) and hypertension. Bosentan is a dual endothelin receptor antagonist effective in the treatment of pulmonary arterial hypertension (PAH), the first of the class to make it to market. Bosentan is an orally available, competitive antagonist of both the ETA and ETB receptor subtypes with a Ki of 4.7 nM for ETA and a Ki of 95 nM for ETB.
in vitro
a study was performed in vitro to measure the influence of bosentan on the angiogenic performance of dermal microvascular endothelial cells (mvecs) and to detect the capacity of bosentan in offsetting the antiangiogenic effects of systemic sclerosis sera. it was found that bosentan significantly increased cell viability and offset the antiangiogenic effects of systemic sclerosis sera on dermal mvecs. [2]
in vivo
a study was conducted to investigate the effect of bosentan on plasma leptin level after myocardial infarction in wistar rats. after oral administration of bosentan once daily at the dose of 100 mg/kg for 2 days, concentration of leptin in plasma significantly increased. this finding revealed that bosentan played an crucial role on regulating leptin concentration in ischemic cardiovascular pathology. [1]
IC 50
inhibiting endothelin receptor a and b with an ic50 of 15.1 ± 1.6 μm in p388/dx cells.
References
[1] ostrowski rp, januszewski sa, kowalska za and kapuscinski a. effect of endothelin receptor antagonist bosentan on plasma leptin concentration in acute myocardial infarction in rats. pathophysiology. 2003 sep; 9(4): 249-56.
[2]romano e, bellando-randone s, manetti m, bruni c, lepri g, matucci-cerinic m, guiducci s. bosentan blocks the antiangiogenic effects of sera from systemic sclerosis patients: an in vitro study. clin exp rheumatol. 2015 aug; 33(4 suppl 91): s148-52.
[3]rubin lj, badesch db, barst rj, galiè n, black cm et, al. bosentan therapy for pulmonary arterial hypertension. new engl j med. 2002 mar; 346 (12): 896-903.
