title: Cherry-picked ligands at histamine receptor subtypes.
abstract: Histamine, a biogenic amine, is considered as a principle mediator of multiple physiological effects through binding to its H1, H2, H3, and H4 receptors (H1-H4Rs). Currently, the HRs have gained attention as important targets for the treatment of several diseases and disorders ranging from allergy to Alzheimer's disease and immune deficiency. Accordingly, medicinal chemistry studies exploring histamine-like molecules and their physicochemical properties by binding and interacting with the four HRs has led to the development of a diversity of agonists and antagonists that display selectivity for each HR subtype. An overview on H1-R4Rs and developed ligands representing some key steps in development is provided here combined with a short description of structure-activity relationships for each class. Main chemical diversities, pharmacophores, and pharmacological profiles of most innovative H1-H4R agonists and antagonists are highlighted. Therefore, this overview should support the rational choice for the optimal ligand selection based on affinity, selectivity and efficacy data in biochemical and pharmacological studies. This article is part of the Special Issue entitled 'Histamine Receptors'.
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates. Electronic address: bassem.sadek@uaeu.ac.ae.
authors.forename: Bassem
authors.initials: B
authors.lastname: Sadek
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Universitaetsstr. 1, 40225 Düsseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
mesh_terms: D000818:Animals; D018494:Histamine Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*
chemical_list: D018494:Histamine Agents; D011968:Receptors, Histamine
keywords: Agonists; Antagonists; H1–H4 receptors; Histamine