Novel drug targets for ductus arteriosus manipulation: Looking beyond prostaglandins

Forty years ago, non-steroidal anti-inflammatory drugs were first reported to decrease systemic prostaglandin levels and promote ductus arteriosus (DA) closure. And yet, prolonged patency of the DA (PDA) remains a significant clinical problem, complicated by imperfect therapies and wide variations in treatment strategy. There are few pharmacology-based tools available for treating PDA (indomethacin, ibuprofen, and acetaminophen), or for maintaining DA patency (PGE1) as is needed to facilitate corrective surgery for ductus-dependent congenital heart defects. Unfortunately, all of these treatments are inefficient and are associated with concerning adverse effects. This review highlights novel potential DA drug targets that may expand our therapeutic repertoire beyond the prostaglandin pathway.