Alprostadil is a synthetic variant of the biological compound Prostaglandin E1 (PGE1). Prostaglandins are potent vasodilators and are used extensively in treating patients with Pulmonary Arterial Hypertension (PAH). Alprostadil can also be used in treatment of erectile dysfunction, in improving blood flow through the ductus arteriosus of a developing fetus; and improving pulmonary circulation in infants. It is chemically known as (1R,2R,3R)-3-Hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane heptanoic acid.
How Alprostadil Works
Prostaglandin is biosynthesized in the human vascular tissues easily, and has a paracrine mode of signaling on localized G protein-coupled receptors on endothelial cells and platelets. Those on the platelets get activated upon binding to prostaglandin, which in turn activates adenylyl cyclase to produce cAMP, which then prevents any undue platelet activation and counteracts production of excess calcium. Meanwhile, binding of prostaglandin to G protein-coupled receptors on endothelial cells also increases cAMP levels in the cytosol, the latter activating protein kinase A (PKA). PKA is then involved in a series of dephosphorylation reactions, which eventually causes the smooth muscles to relax and paves way for vasodilation. Alprostadil, a synthetic analogue of prostaglandin, works in a similar way when administered externally. It dilates the systemic and pulmonary vascular beds which eases the growing blood pressure and reduces clinical progression.
Alprostadil Clinical Trials
The efficacy of PGE1 in intravenous and inhaled formulations has been a topic of clinical research for a long time. Previous studies have shown that inhaled and intravenously infused alprostadil reduced mean pulmonary arterial pressure (MPAP), improved five-year survival rates in patients with functional class I and II PAH, and reduced endothelin levels. Use has been associated with improved exercise abilities and improved quality of life in people with post-operative PAH. No major side-effects have been observed with infused formulations of aprostadil, leaving minor allergies at the site of infusion.
While Caverject, Muse and Edex (injections) have been marketed as standard FDA approved therapies for treating erectile dysfunction, no formal drug has been marked as such for PAH.