title: Histamine receptors and antihistamines: from discovery to clinical applications.
abstract: 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.
authors.affiliation: Department of Neuroscience, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cataldi
authors.forename: Francesco
authors.initials: F
authors.lastname: Borriello
authors.forename: Francescopaolo
authors.initials: F
authors.lastname: Granata
authors.forename: Lucio
authors.initials: L
authors.lastname: Annunziato
authors.forename: Gianni
authors.initials: G
authors.lastname: Marone
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006633:Histamine Antagonists / Q000138:chemical synthesis / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D008407:Mast Cells / Q000378:metabolism; D011968:Receptors, Histamine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine