Multiple Targeting Approaches on Histamine H3 Receptor Antagonists.
With the very recent market approval of pitolisant (Wakix®), the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 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 H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.
Stark Lab, Institut fuer Pharmazeutische and Medizinische Chemie, Heinrich-Heine-Universitaet DuesseldorfDuesseldorf, Germany; Faculty of Pharmacy, The University of JordanAmman, Jordan.
Mohammad A
MA
Khanfar
Stark Lab, Institut fuer Pharmazeutische and Medizinische Chemie, Heinrich-Heine-Universitaet Duesseldorf Duesseldorf, Germany.
Anna
A
Affini
Stark Lab, Institut fuer Pharmazeutische and Medizinische Chemie, Heinrich-Heine-Universitaet Duesseldorf Duesseldorf, Germany.
Kiril
K
Lutsenko
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade Belgrade, Serbia.
Katarina
K
Nikolic
Department of Biotechnology, Chemistry, and Pharmacy, European Research Centre for Drug Discovery and Development, University of Siena Siena, Italy.
Stefania
S
Butini
Stark Lab, Institut fuer Pharmazeutische and Medizinische Chemie, Heinrich-Heine-Universitaet Duesseldorf Duesseldorf, Germany.
Holger
H
Stark
GPCR; NO; enzymes; histamine; multiple targeting; transporter