Ambrisentan for the treatment of pulmonary arterial hypertension.

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Casserly B, Klinger JR

Ambrisentan for the treatment of pulmonary arterial hypertension.

Drug Des Devel Ther. 2009 Feb 6;2:265-80.

PubMed ID

19920913 [ View in PubMed

]

Abstract

Ambrisentan is an endothelin receptor antagonist (ERA) that was recently approved for treatment of pulmonary arterial hypertension (PAH). Endothelin (ET) is a potent vasoconstrictor with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. The biologic effects of ET are mediated by 2 cell surface receptors termed ET(A) and ET(B). ET(A) mediates the vasoconstrictor effect of ET on vascular smooth muscle, whereas ET(B) is expressed primarily on vascular endothelial cells where it induces nitric oxide synthesis and acts to clear ET from the circulation. Ambrisentan is the first ET(A) selective ERA approved for use in the US. Recently published clinical trials in patients with PAH demonstrate improvement in functional capacity and pulmonary hemodynamics similar to other ET(A) selective and non-selective ERAs. Its once daily dosing and lower incidence of serum aminotransferase elevation offer potential advantages over other ERAs, but further experience with this agent is needed to fully understand its long-term efficacy and safety. This review discusses the endothelin family of proteins and receptors and their role in the pathophysiology of pulmonary hypertensive diseases. It also examines the development process, safety profile and clinical trials that have resulted in ambrisentan being approved for treatment of PAH.

DrugBank Data that Cites this Article

Drugs

Ambrisentan

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ambrisentan	Endothelin B receptor	Protein	Humans	No	Antagonist	Details
Ambrisentan	Endothelin-1 receptor	Protein	Humans	Yes	Antagonist	Details