ACT-132577

ACT-132577 is a pharmacologically active metabolite of macitentan, a dual endothelin receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). ACT-132577 is primarily responsible for the therapeutic effects of macitentan, exerting its effects by blocking the action of endothelin, a vasoconstrictive peptide.

Pharmacology

ACT-132577 works by antagonizing the endothelin receptor, a G-protein coupled receptor found in the endothelium of blood vessels. Endothelin is a potent vasoconstrictor, and by blocking its action, ACT-132577 helps to reduce blood pressure and improve blood flow in patients with PAH.

Metabolism

ACT-132577 is formed in the body through the metabolic breakdown of macitentan. This process is primarily mediated by the cytochrome P450 enzyme system, specifically CYP3A4. Once formed, ACT-132577 is further metabolized and eventually excreted in the urine.

Clinical Use

ACT-132577, as a metabolite of macitentan, is used in the treatment of PAH. It has been shown to improve exercise capacity and delay clinical worsening in patients with this condition. The drug is generally well-tolerated, with the most common side effects being nasopharyngitis, headache, and anemia.

Research

Research into ACT-132577 is ongoing, with studies investigating its pharmacokinetics, pharmacodynamics, and potential uses in other conditions characterized by endothelin overactivity.

See Also

• Macitentan
• Endothelin receptor antagonist
• Pulmonary arterial hypertension