Background: Histamine is a chemical transmitter widely distributed in the human
body. It exerts its effects through the interaction with histaminergic receptors (H1R to
H4R). The H4R is mainly expressed in hematopoietic cells, especially those involved in
immune and inflammatory responses, and thus it is an important target for novel antiinflammatory
agents for the treatment of disorders such as asthma, dermatitis, rheumatoid
arthritis, peritonitis, inflammatory bowel disease and allergic rhinitis. Current pharmacological
therapy for the treatment of such inflammatory disorders includes poorly effective
drugs in many cases, also causing important adverse reactions. Accordingly, the development
of new drugs has been widely explored, especially those with a different mechanism
of action from NSAIDs and corticosteroids.
Discussion: H4R antagonists/inverse agonists have demonstrated potential anti-inflammatory properties and
thus several ligands have been reported, showing efficacy in several clinical and preclinical studies. The
indolcarboxamides, aminopyrimidines, quinoxalines and quinazolines have been the most critically explored
scaffolds to achieve highly selective and potent antagonists/inverse agonists. These derivatives have shown in
vivo activity and important contributions for the structure-activity relationship data.
Conclusion: In this paper, a review of the main ligands is undertaken and reported in the literature showing in
vivo anti-inflammatory activity and potential therapeutic application.