The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines

Nat Rev Drug Discov. 2008 Jan;7(1):41-53. doi: 10.1038/nrd2465.


Histamine has a key role in allergic inflammatory conditions. The inflammatory responses resulting from the liberation of histamine have long been thought to be mediated by the histamine H1 receptor, and H1-receptor antagonists--commonly known as antihistamines--have been used to treat allergies for many years. However, the importance of histamine in the pathology of conditions such as asthma and chronic pruritus may have been underestimated. Here, we review accumulating evidence suggesting that histamine indeed has roles in inflammation and immune function modulation in such diseases. In particular, the discovery of a fourth histamine receptor (H4) and its expression on numerous immune and inflammatory cells has prompted a re-evaluation of the actions of histamine, suggesting a new potential for H4-receptor antagonists and a possible synergy between H1 and H4-receptor antagonists in targeting various inflammatory conditions.

Publication types

  • Review

MeSH terms

  • Arthritis / physiopathology
  • Drug Design
  • Histamine / blood
  • Histamine / physiology*
  • Histamine H1 Antagonists / therapeutic use*
  • Hypersensitivity / drug therapy
  • Hypersensitivity / physiopathology*
  • Inflammation / drug therapy*
  • Ligands
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Histamine / physiology*
  • Receptors, Histamine H1 / physiology*
  • Receptors, Histamine H4


  • HRH4 protein, human
  • Histamine H1 Antagonists
  • Ligands
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H1
  • Receptors, Histamine H4
  • Histamine