Prostaglandin D2 receptor antagonists in allergic disorders: safety, efficacy, and future perspectives

Introduction: Prostaglandin D-2 (PGD(2)) is a major cyclooxygenase mediator that is synthesized by activated human mast cells and other immune cells. The biological effects of PGD(2) are mediated by D-prostanoid (DP1), DP2 (CRTH2) and thromboxane prostanoid (TP) receptors that are expressed on several immune and non-immune cells involved in allergic inflammation. PGD(2) exerts various proinflammatory effects relevant to the pathophysiology of allergic disorders. Several selective, orally active, DP2 receptor antagonists and a small number of DP1 receptor antagonists are being developed for the treatment of allergic disorders. Areas covered: The role of DP2 and DP1 receptor antagonists in the treatment of asthma and allergic rhinitis. Expert opinion: Head-to-head studies that compare DP1 antagonists with the standard treatment for allergic rhinitis are necessary to verify the role of these novel drugs as mono- or combination therapies. Further clinical trials are necessary to verify whether DP2 antagonists as monotherapies or, more likely, as add-on therapies, will be effective for the treatment of different phenotypes of adult and childhood asthma. Long-term studies are necessary to evaluate the safety of targeted anti-PGD(2) treatments.