Histamine Receptors: Ligand Design, Pharmacology, and Therapeutic Applications

A Special Issue of Pharmaceuticals (ISSN 1424-8247) belonging to the section "Pharmacology".

Deadline for manuscript submissions: 30 December 2026 | Viewed by 1721

Editors


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Guest Editor
Department of Synthesis and Technology of Drugs, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Łódź, Poland
Interests: medicinal chemistry; drug discovery; organic synthesis; heterocyclic synthesis; multi-target ligands; histamine; H3 ligands; H1 ligands; guinea pig ex vivo assay
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Synthesis and Technology of Drugs, Medical University of Lodz, ul. Muszyńskiego 1, 90-145 Łódź, Poland
Interests: medicinal chemistry; drug discovery; organic synthesis; heterocyclic synthesis; multi-target ligands; histamine; H3 ligands; H1 ligands; guinea pig ex vivo assay
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Histamine receptors are one of the most studied G protein-coupled receptors (GPCRs) and play crucial roles in various physiological and pathophysiological conditions, including allergic reactions (H1R), gastric acid secretion (H2R), cognitive functions, and CNS disorders, by modulating histamine and other neurotransmitter release (H3R) or inflammatory conditions (H4R). Furthermore, multi-target directed ligands (MTDLs) have become a significant target for diseases with complex pathogenesis.

This Special Issue aims to discuss cutting-edge advancements in research on histamine receptors and the role of new biologically active agents in novel therapeutic strategies, thereby expanding the knowledge of medicinal chemistry. We would like to publish studies that contribute to ligand design, synthesis, and understanding of the relationship between structure and activity (SAR), mode of action, and therapeutic applications. We encourage scientists to share both original and computational results of their research, as well as comprehensive reviews and short communications concerning histamine receptors and their ligands in this Special Issue. Furthermore, we believe that our Special Issue will inspire the scientific community worldwide. The subtopics may include a wide range of topics, but are not limited to the following:

  • Design, synthesis, and structural modification of histamine receptor ligands;
  • SAR of the histamine ligands;
  • Target-based drug discovery;
  • Pharmacological or pharmacokinetic evaluation of novel potent lead compounds and biologically active molecules;
  • Alternative therapeutics: novelty and hopes;
  • Multifunctional histamine receptor ligands in medicinal chemistry;
  • Molecular mechanisms underlying the pharmacological actions of histamine ligands;
  • Computational studies of histamine ligands that provide insight into the SAR of the novel molecules.

Dr. Marek Staszewski
Prof. Dr. Krzysztof Walczyński
Guest Editors

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Keywords

  • histamine receptors
  • drug discovery
  • ligand design
  • antagonist/inverse agonist
  • pharmacology
  • therapeutic applications
  • multi-target directed ligands
  • molecular modeling

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Published Papers (1 paper)

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Research

20 pages, 3648 KB  
Article
Histamine H1 Receptor-Mediated CREB Phosphorylation via Gq Protein Signaling and Arrestin Modulation
by Ryosuke Ogami, Shotaro Michinaga, Yosuke Iiboshi, Yasuhiro Ogawa and Shigeru Hishinuma
Pharmaceuticals 2026, 19(2), 227; https://doi.org/10.3390/ph19020227 - 28 Jan 2026
Viewed by 1307
Abstract
Background/Objectives: Histamine H1 receptors mediate multiple physiological and pathophysiological processes, including inflammation and allergy, by regulating downstream gene expression via transcription factors. cAMP response element-binding protein (CREB) is a major transcription factor whose phosphorylation is regulated by multiple signaling pathways. Although [...] Read more.
Background/Objectives: Histamine H1 receptors mediate multiple physiological and pathophysiological processes, including inflammation and allergy, by regulating downstream gene expression via transcription factors. cAMP response element-binding protein (CREB) is a major transcription factor whose phosphorylation is regulated by multiple signaling pathways. Although CREB is closely involved in multiple physiological and pathophysiological processes, the detailed intracellular signaling pathway of H1 receptor-mediated CREB phosphorylation remains to be elucidated. We investigated the roles of Gq proteins and arrestins in H1 receptor-mediated CREB phosphorylation. Methods: We constructed Chinese hamster ovary (CHO) expressing human wild-type (WT) H1 receptors and two types of C-terminal mutants. One mutant was constructed by truncating the serine 487 residue only at the C-terminus (S487Trunc), and the other was constructed by substituting the serine 487 residue at the C-terminus with alanine (S487A). S487Trunc is a Gq protein-biased while S487A is an arrestin-biased receptor. The expressions of CREB and its phosphorylated form were assessed by immunoblotting. Results: Histamine promoted CREB phosphorylation in CHO cells expressing WT or S487Trunc receptors, but not in cells expressing S487A. Inhibitors of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), or c-Jun N-terminal kinase (JNK), and Ca2+ chelator suppressed histamine-induced CREB phosphorylation in CHO cells expressing WT or S487Trunc receptors. Basal CREB phosphorylation levels increased following β-arrestin overexpression and decreased after their siRNA-mediated knockdown, thus modulating histamine-stimulated CREB phosphorylation in WT CHO cells. Conclusions: H1 receptor-mediated CREB phosphorylation is induced through Gq protein/Ca2+/PKC-dependent ERK and JNK activation; arrestins can modulate this process by regulating basal CREB phosphorylation. Full article
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