Histamine H4 Receptor: A Novel Target for Inflammation Therapy

Histamine, a low molecular weight amine has been extensively studied for its various pharmacological profiles. Until recently histamine was thought to act on three receptors - H-1, H-2 and H-3. Merely a decade back, sequencing of human genome has revealed a new histamine receptor - H-4 receptor. This 390 amino acid sequenced receptor has around 38% homology with histamine H-3 receptor besides; the pharmacological profile of the protein is quite different from other histamine receptors. H-4 receptor is mainly expressed in mast cells and leukocytes and involves various physiological functions related to inflammation and allergy. Potent selective H-4 receptor agonists and antagonists have been synthesized and in vivo studies have indicated their action on H-4 receptor. In this review, structure, expression, homology sequence of H-4 receptor among the different species have been documented. Further, structure activity relationship (SAR) of H-4 and ligands on the basis of their nucleus has been discussed in depth. In addition, anti-inflammatory effects of H-4 receptor antagonists, with special emphasis to JNJ7777120, a selective H-4 receptor antagonist have been focused exhaustively.