Molecular Aspects of Histamine Receptors

Mocking, Tamara A. M.; Bosma, Reggie; Rahman, Sabrina N.; Verweij, Eléonore W E; McNaught-Flores, Daniel A.; Vischer, Henry F.; Leurs, Rob

doi:10.1007/978-3-319-40308-3_1

Cited by 6 publications

(16 citation statements)

References 282 publications

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“…High‐affinity H 3 R and H 4 R are expressed mostly on neurons and immune cells, and respond to histamine in the ng/mL range. More detail information is reviewed by Mocking et al…”

Section: Introductionmentioning

confidence: 99%

“…Increased intracellular Ca 2+ concentration leads to activation of specific PKC isoforms, smooth muscle contraction, nitric oxide (NO) synthase‐induced vasodilatation, and stimulation of phospholipase A 2 (PLA 2 ) to produce arachidonic acid. Ca 2+ binding to calmodulin further activates transcription factors (nuclear factor of activated T cells, nuclear factor‐κB) promoting the transcription of cytokines …”

Section: Introductionmentioning

confidence: 99%

“…Preclinical studies using H 3 R inverse agonist and antagonist have shown efficacy in reducing allodynia and hyperalgesia in neuropathic and inflammatory pain . Loss of H 3 R function results in locomotion reduction, hyperphagia, obesity, and neuroinflammation . As a result of alternative splicing, at least 20 isoforms have been identified.…”

Section: Introductionmentioning

confidence: 99%

“…To more specifically target the H 3 R, Guerrero et al utilized methylated histamine. Methylation of the ethylamine side chain of histamine (N α ‐methylhistamine) potentiates its binding to H 3 Rs (H 3 Ki 0.36‐0.6 nM), but slightly decreases binding to H 1 R, H 2 R, and H 4 R . High dose N α ‐methylhistamine (20 mg/kg s.c.) can still stimulate H 1 Rs and H 2 Rs.…”

Section: Introductionmentioning

confidence: 99%

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Histamine and Migraine

Yuan

Silberstein

2017

Headache

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Background Histamine is an ancient “tissue amine” preceding multicellular organisms. In the central nervous system (CNS), its fibers originate solely from the tuberomammillary nucleus and travel throughout the brain. It is mainly responsible for wakefulness, energy homeostasis, and memory consolidation. Recently, several studies suggest a potential role of histamine in migraine pathogenesis and management. Methods Narrative review of current literature regarding histamine and migraine. Results Histamine plays a crucial role in migraine pathogenesis: sustaining the neurogenic inflammation pathway. Interaction between mast cells (MC) and calcitonin‐gene related protein (CGRP) results in sensitization of trigeminal afferents and trigeminal ganglia (TG). Histamine binds with differing affinities to four different histaminergic G‐protein coupled receptors, activating protein kinases, or triggering calcium release with subsequent mode of actions. Histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists are frequently used for the treatment of allergy and gastric acid secretion, respectively, but their antagonism is probably ineffective for migraine. Histamine 3 receptor (H3R) and histamine 4 receptor (H4R) have a threefold higher affinity than H1R/H2R for histamine and are found almost exclusively on neurons and immune tissues, respectively. H3R acts as an autoreceptor or as a heteroreceptor, lowering the release of histamine and other neurotransmitters. This is a potential target for anti‐nociception and anti‐neurogenic inflammation. To date, several small clinical trials using low dose histamine or Nα‐methylhistamine have demonstrated migraine prophylactic efficacy, probably via H3R or other undetermined pathways. Conclusion The histamine system interacts with multiple regions in the CNS and may hypothetically modulate the migraine response. Low dose histamine may be a promising option for migraine prevention.

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“…High‐affinity H 3 R and H 4 R are expressed mostly on neurons and immune cells, and respond to histamine in the ng/mL range. More detail information is reviewed by Mocking et al…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Histamine and Migraine

Yuan

Silberstein

2017

Headache

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“…As presynaptic autoreceptors, they not only control the release of histamine, but also regulate the release of other neurotransmitters such as dopamine, norepinephrine, serotonin, and acetylcholine (Berlin, Boyce, & Ruiz, ). From sequence similarity point of view, H 3 R shows the highest sequence homology to the H 4 R (about ~37%) while less than 20% to H 1 and H 2 receptors (Mocking et al., ; Tiligada, Zampeli, Sander, & Stark, ). H 3 R are mainly found in central nervous system (CNS) of human and animals.…”

Section: Introductionmentioning

confidence: 99%

Histamine H₃ receptor ligands by hybrid virtual screening, docking, molecular dynamics simulations, and investigation of their biological effects

et al. 2019

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Histamine H3 receptors (H3R), belonging to G‐protein coupled receptors (GPCR) class A superfamily, are responsible for modulating the release of histamine as well as of other neurotransmitters by a negative feedback mechanism mainly in the central nervous system (CNS). These receptors have gained increased attention as therapeutic target for several CNS related neurological diseases. In the current study, we aimed to identify novel H3R ligands using in silico virtual screening methods. To this end, a combination of ligand‐ and structure‐based approaches was utilized for screening of ZINC database on the homology model of human H3R. Structural similarity‐ and pharmacophore‐based approaches were employed to generate compound libraries. Various molecular modeling methodologies such as molecular docking and dynamics simulation along with different drug likeness filtering criteria were applied to select anti‐H3R ligands as promising candidate molecules based on different known parent lead compounds. In vitro binding assays of the selected molecules demonstrated three of them being active within the micromolar and submicromolar Ki range. The current integrated computational and experimental methods used in this work can provide new general insights for systematic hit identification for novel anti‐H3R agents from large compound libraries.

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Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated pathways

Rahman,

Imhaouran,

Leurs

et al. 2024

Biochemical Pharmacology

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Molecular Aspects of Histamine Receptors

Cited by 6 publications

References 282 publications

Histamine and Migraine

Histamine and Migraine

Histamine H₃ receptor ligands by hybrid virtual screening, docking, molecular dynamics simulations, and investigation of their biological effects

Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated pathways

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Molecular Aspects of Histamine Receptors

Cited by 6 publications

References 282 publications

Histamine and Migraine

Histamine and Migraine

Histamine H3 receptor ligands by hybrid virtual screening, docking, molecular dynamics simulations, and investigation of their biological effects

Ligand-directed biased agonism at human histamine H3 receptor isoforms across Gαi/o- and β-arrestin2-mediated pathways

Contact Info

Product

Resources

About

Histamine H₃ receptor ligands by hybrid virtual screening, docking, molecular dynamics simulations, and investigation of their biological effects