Progress in the development of histamine H₃ receptor antagonists/inverse agonists: a patent review (2013-2017)

Since years, ligands blocking histamine H₃ receptor (H₃R) activity (antagonists/inverse agonists) are interesting targets in the search for new cures for CNS disorders. Intensive works done by academic and pharmaceutical company researchers have led to many potent and selective H₃R antagonists/inverse agonists. Some of them have reached to clinical trials.

Patent applications from January 2013 to September 2017 and the most important topics connected with H₃R field are analysed. Espacenet, Patentscope, Pubmed, GoogleScholar or Cochrane Library online databases were principially used to collect all the materials.

The research interest in histamine H₃R field is still high although the number of patent applications has decreased during the past 4 years (around 20 publications). Complexity of histamine H₃R biology e.g. many isoforms, constitutive activity, heteromerization with other receptors (dopamine D₂, D₁, adenosine A_2A) and pharmacology make not easy realization and evaluation of therapeutic potential of anti-H₃R ligands. First results from clinical trials have verified potential utility of histamine H₃R antagonist/inverse agonists in some diseases. However, more studies are necessary for better understanding of an involvement of the histaminergic system in CNS-related disorders and helping more ligands approach to clinical trials and the market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor; hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase; MAO - monoamine oxidase.