Ambrisentan

( S) -2 - (4,6- dimethylpyrimidin -2 -yloxy) -3-methoxy -3 ,3- diphenylpropionic acid (IUPAC)

C02KX02

Endothelin receptor antagonist

Endothelin is selectively repressed by his ET1A receptors, this results in a vasodilatation and a (pulmonary ) blood pressure reduction

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Ambrisentan is a drug from the group of endothelin receptor antagonists. It is used to treat a rare form of high blood pressure is elevated in the blood pressure in the blood vessels that carry blood from the heart to the lungs flows ( pulmonary hypertension, pulmonary arterial hypertension ( PAH) classified as WHO functional class II and III).

For this application it is under the trade name Volibris ® (manufacturer GlaxoSmithKline ( GSK) ) approved in the European Union and in Switzerland since 2008.

Ambrisentan and is, as well as the endothelin receptor antagonist bosentan and Thelin, classified as an orphan drug.

Pharmacology

Mechanism of Action

Ambrisentan displaced as an antagonist endothelin -1, the strongest known endogenous Blutgefäßkonstringenz selectively from his ET1A receptors and thus removes the endothelin-1 effect, so that the vessels dilate and so the damage caused by the endothelin increase in the ( pulmonary ) blood pressure counteracted, and there is a ( pulmonary ) reduction in blood pressure. Due to the selectivity results in an advantage over the non-selective bosentan, as caused by the ET1B receptors effects, the production of the vasodilators nitric oxide ( NO) and prostacyclin, are unaffected and so can cause an additional dilatation. In addition, as the injury caused by endothelin changes in the blood vessels ( remodeling ) is counteracted.

Side effects

Side effects may occur as a result of the intervention in the regulation of blood pressure to headache, reddening of the skin, and peripheral edema as disorders of the gastrointestinal tract ( nausea and abdominal pain) and sinusitis -like symptoms with nasal congestion are possible.

Contraindications

Contraindications represent a pregnancy and liver dysfunction associated with elevated liver transaminases. In July 2012, the manufacturer GSK pointed out in a Red Hand Letter indicate that ambrisentan should not be used in patients with idiopathic pulmonary fibrosis ( IPF).

Studies

Phase III trials - ARIES-1 and ARIES -2