Histamine receptors and antihistamines: From discovery to clinical applications

The synthesis and the identification of histamine marked a milestone in both pharmacological and immunological research. Since Sir Henry Dale and Patrick Laidlaw described some of its physiological effects in vivo in 1910, histamine has been shown to play a key role in the control of gastric acid secretion and in allergic disorders. Using selective agonists and antagonists, as well as molecular biology tools, four histamine receptors (H₁R, H₂R, H₃R and H₄R) have been identified. The Nobel Prize in Physiology and Medicine was awarded to Daniel Bovet in 1957 for the discovery of antihistamines (anti-H₁R) and to Sir James Black in 1988 for the identification of anti-H₂R antagonists. Anti-H₁R and anti-H₂R histamine receptor antagonists have revolutionized the treatment of certain allergic disorders and gastric acid-related conditions, respectively. More recently, anti-H₃R antagonists have entered early-phase clinical trials for possible application in obesity and a variety of neurologic disorders. The preferential expression of H₄R by several immune cells and its involvement in the development of allergic inflammation provide the rationale for the use of anti-H₄R antagonists in allergic and in other immune-related disorders.