AUTHOR=Khanfar Mohammad A. , Affini Anna , Lutsenko Kiril , Nikolic Katarina , Butini Stefania , Stark Holger 

TITLE=Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

JOURNAL=Frontiers in Neuroscience

VOLUME=10

YEAR=2016

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2016.00201

DOI=10.3389/fnins.2016.00201

ISSN=1662-453X

ABSTRACT=<p>With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H<sub>3</sub> receptor antagonists has clearly increased. Since histamine H<sub>3</sub> receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H<sub>3</sub> receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.</p>