Ambrisentan, sold under the brand name Letairis among others, is a drug used for the treatment of

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

. It is an endothelin receptor antagonist. The peptide

endothelin Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute ...

constricts muscles in blood vessels, increasing blood pressure. Ambrisentan, which relaxes those muscles, is an

endothelin receptor antagonist An endothelin receptor antagonist (ERA) is a drug that blocks endothelin receptors. Three main kinds of ERAs exist: * Dual ET Receptor Antagonists, which affect both endothelin A (ETA) and B receptors (ETB)CPU0213 21780-32-9is an example of a ...

, and is selective for the type A

endothelin receptor There are at least four known endothelin receptors, ETA, ETB1, ETB2 and ETC, all of which are G protein-coupled receptors whose activation result in elevation of intracellular-free calcium, which constricts the smooth muscles of the blood vessels ...

(ET_A). Ambrisentan significantly improved exercise capacity (6-minute walk distance) compared with placebo in two double-blind, multicenter trials (ARIES-1 and ARIES-2). Like all endothelin receptor antagonists, Ambrisentan is contraindicated in pregnant women as well as those who are trying to become pregnant, due to the potential for

teratogenic Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology caused by ...

effects on the fetus. Ambrisentan was approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) and the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA), and designated an

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

, for the treatment of pulmonary hypertension.

Medical uses

Ambrisentan is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of pulmonary arterial hypertension (WHO Group 1) in people with WHO class II or III symptoms to improve exercise capacity and delay clinical worsening.

Mechanism of action

Ambrisentan is a drug that blocks endothelin, an endogenous hormone found in higher quantities in patients with pulmonary arterial hypertension. Endothelin binds to two receptors, ET_A and ET_B. ET_A is responsible for cell growth in the vessels as well as

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

, while ET_B plays a role in

vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...

endothelin 1 Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor peptide produced by vascular endothelial cells, as well as by cells in the heart (affecting contractility) and kidney (affecting sodium handling). The protei ...

clearance, and anti proliferation of cells.

Birth defects

Endothelin receptor activation mediates strong pulmonary

and positive

inotropic An inotrope or inotropic is a drug or any substance that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular co ...

effect on the heart. These physiologic effects are vital for the development of the fetal cardiopulmonary (heart and lung) system. In addition to this, endothelin receptors are also known to play a role in

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

cell migration, growth, and differentiation. As such, endothelin receptor antagonists such as ambrisentan are known to be teratogenic.

Society and culture

Brand names

Ambrisentan is sold under the brand name Letairis, Volibris, and Pulmonext.

Publications

References

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