Background: The histamine H4 receptor (H4R) was first cloned in 2000. As a new member of the histamine receptor family it was of great interest and a promising drug target for the treatment of inflammatory diseases. Recent studies suggest that H4 antagonists have therapeutic potential, even in several pain conditions. Initially, pharmacological processes mediated by H4R were analyzed primarily by non-selective H4 ligands. Since then, some highly potent and selective H4 antagonists have been reported by different groups. Several companies are working on the development of potent H4 antagonists, although the number of published patent applications is still low.
Objective: This review aims to give an overview of the ligands acting on H4R, this is drawn from published in papers and patent applications.
Methods: Analysis of scaffolds possessing significant H4 activity and review of their therapeutic potential.
Results/conclusion: The pharmacology of currently available selective H4 ligands suggests therapeutic utility for H4 antagonists in inflammatory conditions as well as in chronic pain.