Histamine H4 receptor agonists

Since its discovery 10 years ago the histamine H-4 receptor (H4R) has attracted attention as a potential drug target, for instance, for the treatment of inflammatory and allergic diseases. Potent and selective ligands including agonists are required as pharmacological tools to study the role of the H4R in vitro and in vivo. Many H4R agonists, which were identified among already known histamine receptor ligands, show only low or insufficient H4R selectivity. In addition, the investigation of numerous H4R agonists in animal models is hampered by species-dependent discrepancies regarding potencies and histamine receptor selectivities of the available compounds, especially when comparing human and rodent receptors. This article gives an overview about structures, potencies, and selectivities of various compounds showing H4R agonistic activity and summarizes the structure-activity relationships of selected compound classes. (C) 2010 Elsevier Ltd. All rights reserved.