Antihistamine
The vast majority of marketed H-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor. Clinically, H-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation is a common side effect of H-antihistamines that readily cross the blood–brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia. H-antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor the regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist (i.e., histamine) binding at the H receptor.
Antihistamine
The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.