Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [15,38]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [15]. The human and rat H₃ receptor genes are subject to significant splice variance [3]. The potency order of histamine at histamine receptor subtypes is H₃ = H₄ > H₂ > H₁ [38]. Some agonists at the human H₃ receptor display significant ligand bias [43]. Antagonists of all 4 histamine receptors have clinical uses: H₁ antagonists for allergies (e.g. cetirizine), H₂ antagonists for acid-reflux diseases (e.g. ranitidine), H₃ antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H₄ antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [38] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [1,49].

Histaprodifen and methylhistaprodifen are reduced efficacy agonists. The H₄ receptor appears to exhibit broadly similar pharmacology to the H₃ receptor for imidazole-containing ligands, although (R)-α-methylhistamine and N-α-methylhistamine are less potent, while clobenpropit acts as a reduced efficacy agonist at the H₄ receptor and an antagonist at the H₃ receptor [27,35-37,52]. Moreover, 4-methylhistamine is identified as a high affinity, full agonist for the human H₄ receptor [26]. [³H]Histamine has been used to label the H₄ receptor in heterologous expression systems.

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Subcommittee members: Paul Chazot (Co-chairperson) School of Biological and Biomedical Sciences Durham University South Road Durham DH1 3LE UK Rob Leurs (Co-chairperson) Leiden/Amsterdam Center for Drug Research (LACDR) Division of Medicinal Chemistry Faculty of Science VU University Amsterdam De Boelelaan 1083 1081 HV Amsterdam The Netherlands Marlon Cowart Dept. Neuroscience Research Abbott Laboratories AP9a/216, GPRD_R4MN 100 Abbott Park Road IL 60064-6123 Abbott Park USA Ralf Gutzmer Hannover Medical School Dept. of Dermatology 30449 Hannover Germany Helmut L. Haas Department of Physiology Heinrich Heine University Dusseldorf W-40001 Germany Steve Liu Pfizer Global Research & Development Kent UK Pertti Panula Biomedicum Helsinki P.O. Box 63 FIN-00014 University of Helsinki Jean-Charles Schwartz Unité de Neurobiologie et Pharmacologie Moléculaire INSERM U109 Centre Paul Broca 2ter rue d'Alésia Paris 75014 France Roland Seifert Institute of Pharmacology Medical School of Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Holger Stark Goethe University Institute of Pharmaceutical Chemistry ZAFES/CMP/ICNP Max-von-Laue Str. 9 60438 Frankfurt/Main Germany Robin Thurmond Johnson & Johnson Pharmaceutical Research & Development 3210 Merryfield Row San Diego CA 92121 USA

Other contributors: Hiroyuki Fukui Department of Pharmacology The University of Tokushima Faculty of Pharmaceutical Sciences Tokushima 770-0044 Japan C. Robin Ganellin Department of Chemistry Christopher Ingold Laboratories University College London 20 Gordon Street London WC1H 0AJ UK Stephen J. Hill (Past chairperson) Institute of Cell Signalling Medical School Queen's Medical Centre Nottingham NG7 2UH UK Rebecca Hills (Past curator) Roberto Levi Department of Pharmacology Cornell University Medical College 1300 York Avenue New York NY 10021 USA Walter Schunack Institut fur Pharmazie Freie Universitat Berlin Konigin-Luise-Strasse 2 and 4 Berlin D-14195 Germany Nigel P. Shankley R. W. Johnson Pharmaceutical Research Institute 3210 Merryfield Row San Diego CA 92121 USA Henk Timmerman Department of Pharmacology Leiden-Amsterdam Center for Drug Research Vrije Universiteit De Boelelaan 1083 Amsterdam 1081 HV The Netherlands J. Michael Young Department of Pharmacology University of Cambridge Tennis Court Road Cambridge CB2 1QJ UK