Abstract:
:With the recent market approval of Pitolisant (Wakix®), the interest in clinical application for novel multifunctional histamine H3 receptor antagonists has clearly increased. Several combinations of different H3R pharmacophores with pharmacophoric elements of other G-protein coupled receptors, transporters or enzymes have been synthesized by numerous pharmaceutical companies and academic institutions. Since central nervous system disorders are characterized by diverse physiological dysfunctions and deregulations of a complex network of signaling pathways, optimal multipotent drugs should simultaneously and peculiary modulate selected groups of biological targets. Interestingly, very recent studies have shown that some of clinically evaluated histamine H3 receptor antagonists possess nanomolar affinity for sigma-1 receptor binding sites, suggesting that this property might play a role in their overall efficacy. The sigma-1 receptor, unusual and yet obscure protein, is supposed to be involved in numerous CNS pathologies through neuroprotection and neuroplasticity. These two different biological structures, histamine H3 and sigma-1 receptors, combined can represent potential fruitful target for therapeutic developments in tackling numerous human diseases.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Szczepańska K,Kuder KJ,Kieć-Kononowicz Kdoi
10.2174/0929867327666200806103144subject
Has Abstractpub_date
2020-08-05 00:00:00eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-108881pub_type
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