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With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H 3  receptor antagonists has clearly increased. Since histamine H 3  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 3  receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

Multiple Targeting Approaches on Histamine H3 Receptor Antagonists