In:
Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 28, No. 15 ( 2021-05), p. 2974-2995
Kurzfassung:
With the recent market approval of Pitolisant (Wakix®), the interest in clinical application
for novel multifunctional histamine H 3 receptor antagonists has clearly increased.
Several combinations of different H 3 R 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 peculiarly
modulate selected groups of biological targets. Interestingly, very recent studies have shown that some clinically evaluated histamine H 3 receptor antagonists possess a 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 H 3 and sigma-1 receptors, combined, can represent
a potential fruitful target for therapeutic developments in tackling numerous human diseases.
Materialart:
Online-Ressource
ISSN:
0929-8673
DOI:
10.2174/0929867327666200806103144
Sprache:
Englisch
Verlag:
Bentham Science Publishers Ltd.
Publikationsdatum:
2021
SSG:
15,3
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