Histamine and Histamine Receptor Ligands

Abstract Histamine belongs to the group of biogenic amines and exerts its biological properties mainly mediated by four different G‐protein‐coupled receptor class A subtypes, named H 1 –H 4 receptors. While selective agonists are mainly used for pharmacological experiments, antagonists are widely used in different therapeutic fields. Different generations of H 1 receptor antagonists are mainly used for the treatment of allergic diseases and sleep disturbances, whereas H 2 receptor antagonists became blockbuster drugs in the treatment of stomach ulcers. With the detection of the H 3 receptor, the neurotransmitter properties of histamine have been proven. Despite several approaches, so far only one H 3 receptor antagonist (Pitolisant) got market approval for the orphan disease narcolepsy and for obstructive sleep apnea. The immunomodulatory and anti‐inflammatory properties of H 4 receptor antagonists have raised hopes for new therapeutic approaches in the near future.