Abstract
Histamine plays an important role as neurotransmitter and chemical mediator in multiple physiological and pathophysiological processes in central and peripheral tissues. In the last century the extensive study of its actions in the human body, resulted in the identification of four G protein-coupled receptor (GPCR) subtypes (H1R-H4R), mediating numerous effects. The successful application of H1R and H2R antagonists/inverse agonists in the treatment of allergic conditions and gastric ulcer proved that these two receptors are excellent drug targets. Ligands for H3R are currently in advanced stages of clinical development for a broad spectrum of mainly central diseases (e.g. narcolepsy, Alzheimer's disease, epilepsy and schizophrenia). Meanwhile, preclinical research in the H4R field, focused on inflammatory and immunological processes, led to the evaluation of the first H4R-targeting clinical candidates. Drug development for each histamine receptor subtype will be discussed with a special focus on H3R and H4R ligands.
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