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 - H1, H2 and H3. Merely a decade back, sequencing of human genome has revealed a new histamine receptor - H4 receptor. This 390 amino acid sequenced receptor has around 38% homology with histamine H3 receptor besides; the pharmacological profile of the protein is quite different from other histamine receptors. H4 receptor is mainly expressed in mast cells and leukocytes and involves various physiological functions related to inflammation and allergy. Potent selective H4 receptor agonists and antagonists have been synthesized and in vivo studies have indicated their action on H4 receptor. In this review, structure, expression, homology sequence of H4 receptor among the different species have been documented. Further, structure activity relationship (SAR) of H4 and ligands on the basis of their nucleus has been discussed in depth. In addition, anti-inflammatory effects of H4 receptor antagonists, with special emphasis to JNJ7777120, a selective H4 receptor antagonist have been focused exhaustively.
Keywords: Agonist, antagonist, G protein-coupled receptor (GPCR), JNJ7777120, histamine H4 receptor, inflammation, Structure activity relationship (SAR), peptic ulcers, gastroesophageal reflux disease, sleep-wake disorder, epilepsy, obesity, depression, dementia, schizophrenia, Alzheimer's disease, attention-deficit hyperactivity disorder (ADHD), neuropathic pain, Antihistamines