Chemical Probes for Histamine Receptor Subtypes

Falkenstein, Markus; Elek, Milica; Stark, Holger

doi:10.1007/7854_2021_254

Cited by 3 publications

(3 citation statements)

References 214 publications

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“…13 ). For example, the ligands for H 2 R and H 3 R have a more linear structure 57 . Furthermore, their binding sites to H 2 R and H 3 R are not as deep as those involved in H 1 R (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of antihistamines recognition and regulation of the histamine H1 receptor

Wang,

Guo,

et al. 2024

Nat Commun

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Histamine receptors are a group of G protein-coupled receptors (GPCRs) that play important roles in various physiological and pathophysiological conditions. Antihistamines that target the histamine H1 receptor (H1R) have been widely used to relieve the symptoms of allergy and inflammation. Here, to uncover the details of the regulation of H1R by the known second-generation antihistamines, thereby providing clues for the rational design of newer antihistamines, we determine the cryo-EM structure of H1R in the apo form and bound to different antihistamines. In addition to the deep hydrophobic cavity, we identify a secondary ligand-binding site in H1R, which potentially may support the introduction of new derivative groups to generate newer antihistamines. Furthermore, these structures show that antihistamines exert inverse regulation by utilizing a shared phenyl group that inserts into the deep cavity and block the movement of the toggle switch residue W4286.48. Together, these results enrich our understanding of GPCR modulation and facilitate the structure-based design of novel antihistamines.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanism of antihistamines recognition and regulation of the histamine H1 receptor

Wang,

Guo,

et al. 2024

Nat Commun

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“…Histamine is an endogenous HR ligand with a moderate to high affinity for HRs: the affinity for H1R and H2R is more than 1000-fold lower than the affinity for H3R and H4R, although this lack of selectivity is a significant disadvantage [ 38 ].…”

Section: General Information On Histaminementioning

confidence: 99%

“…It has also been reported that the effect of JNJ7777120 exposure is highly dependent on the specific species (mice, rats, etc. ), which is important to consider in further studies [ 38 ]. Other selective H4R antagonists also reduced manifestations of chemically induced colitis.…”

Section: Antagonists and Agonists Of Hrs—possible Ibd Therapy?mentioning

confidence: 99%

Inflammatory Bowel Disease: Crosstalk between Histamine, Immunity, and Disease

Dvornikova

Platonova

Bystrova

2023

IJMS

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Inflammatory bowel disease (IBD) is increasingly recognized as a serious, worldwide public health concern. It is generally acknowledged that a variety of factors play a role in the pathogenesis of this group of chronic inflammatory diseases. The diversity of molecular actors involved in IBD does not allow us to fully assess the causal relationships existing in such interactions. Given the high immunomodulatory activity of histamine and the complex immune-mediated nature of inflammatory bowel disease, the role of histamine and its receptors in the gut may be significant. This paper has been prepared to provide a schematic of the most important and possible molecular signaling pathways related to histamine and its receptors and to assess their relevance for the development of therapeutic approaches.

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Investigation of the protective and therapeutic effects of Diphenhydramine in an in vitro Parkinson’s model

Ağarı,

Binzet,

Kara Öztabağ

et al. 2024

Abant Medical Journal

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Objective: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. Due to the rising prevalence of PD, the need for neuroprotective treatments is increasing, and these are being investigated as a means to slow the disease’s progression. Diphenhydramine (DPH), acting as a histamine 1 receptor antagonist, crosses the blood-brain barrier and exerts effects on the central nervous system. Our aim in this study is to evaluate the neuroprotective and therapeutic effects of DPH in an in vitro PD model induced by 6-hydroxydopamine (6-OHDA). Materials and Methods: An in vitro PD model was established in Glioblastoma (U-118 MG) cells using 6-OHDA. DPH was applied at three different concentrations before and after 6-OHDA application. The protective effect of DPH was evaluated by assessing cell viability using the XTT cell proliferation assay. The results were analyzed using statistical analysis methods. Results: Our study demonstrated that dose-controlled administration of DPH has both neuroprotective and therapeutic effects on an in vitro Parkinson’s model established with 6-OHDA in the U-118MG cell line. According to our findings, DPH at concentrations of 1, 10, and 100 µM significantly increased cell viability compared to the 6-OHDA control group. DPH at 1 and 10 µM concentrations showed important potential for therapeutic and neuroprotective use. Conclusions: The in vitro study indicates that DPH has neuroprotective and therapeutic effects on PD-modeled U-118MG neuronal cells by increasing cell viability. Nevertheless, in vivo studies are needed to evaluate the effects of DPH on animal models of PD.

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Chemical Probes for Histamine Receptor Subtypes

Cited by 3 publications

References 214 publications

Molecular mechanism of antihistamines recognition and regulation of the histamine H1 receptor

Molecular mechanism of antihistamines recognition and regulation of the histamine H1 receptor

Inflammatory Bowel Disease: Crosstalk between Histamine, Immunity, and Disease

Investigation of the protective and therapeutic effects of Diphenhydramine in an in vitro Parkinson’s model

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