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

Expert Opin Investig Drugs. 2019 Jan;28(1):73-84. doi: 10.1080/13543784.2019.1555237. Epub 2018 Dec 7.

Abstract

Introduction: Prostaglandin D2 (PGD2) is a major cyclooxygenase mediator that is synthesized by activated human mast cells and other immune cells. The biological effects of PGD2 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. PGD2 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-PGD2 treatments.

Keywords: Asthma; CRTH2; DP2; allergic disorders; fevipiprant; mast cells; prostaglandin D2; rhinitis.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / adverse effects
  • Anti-Allergic Agents / pharmacology
  • Asthma / drug therapy*
  • Asthma / immunology
  • Child
  • Drug Design
  • Humans
  • Mast Cells / immunology
  • Prostaglandin D2 / metabolism
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / metabolism
  • Rhinitis, Allergic / drug therapy*
  • Rhinitis, Allergic / immunology

Substances

  • Anti-Allergic Agents
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostanoid D receptor 1, human
  • Prostaglandin D2
  • prostaglandin D2 receptor