Histamine H4 receptor antagonist reduces dermal inflammation and pruritus in a hapten-induced experimental model

Suwa, Eriko; Yamaura, Katsunori; Oda, Manabu; Namiki, Takao; Ueno, Koichi

doi:10.1016/j.ejphar.2011.05.037

Cited by 42 publications

(42 citation statements)

References 26 publications

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“…This up-regulation of H 4 R expression might be associated with itching that occurs as a rebound phenomenon after withdrawal of high-dose topical glucocorticoids. We confirmed that significant enhancement of pruritus occurred after chronic topical application of dexamethasone in mice (Yamaura et al, 2011). However, further study is needed to investigate the relationship between the expression of H 4 R in skin and pruritus, which are both enhanced by dexamethasone.…”

Section: Expression Of H 4 R In Human Skinsupporting

confidence: 68%

“…We found a significant negative correlation between H 4 R expression in synovial tissues and serum MMP-3 concentration, but no correlation between MMP-3 and H 1 R or H 2 R (Yamaura et al, 2011). These observations suggest that H 4 R is a potential target of novel pharmacotherapeutic agents for RA, and H 4 R functional analysis may be useful in developing such treatments.…”

Section: Wwwintechopencommentioning

confidence: 74%

“…Taken together, these results suggest that histamine H 4 R could be a new drug target for therapeutic use in RA or pruritic skin disorders such as atopic dermatitis. Yamaura K., Doi R., Suwa E., & Ueno K. (2011) The present Edition "Allergic diseases -highlights in the clinic, mechanisms and treatment" aims to present some recent aspects related to one of the most prevalent daily clinical expression disease. The effort of a group of outstanding experts from many countries reflects a set of scientific studies very promising for a better clinical care and also to the treatment and control of the allergy.…”

Section: Resultsmentioning

confidence: 99%

“…Further, we created a chronic itch model in which repeated application of 2,4,6-trinitrochlorobenzene to the back skin of HR-1 mice was seen to elicit frequent scratching behavior at 24 h after challenge. JNJ7777120 at 10 and 30 mg/kg doses reduced this scratching behavior, whereas fexofenadine had no such effect (Suwa et al, 2011). These results suggest that H 4 R antagonists may be useful for treatment of H 1 R antagonist-resistant chronic pruritus such as atopic dermatitis.…”

Section: Effect Of H 4 R Antagonists On Pruritus Modelmentioning

confidence: 99%

See 3 more Smart Citations

Expression of the Histamine H4 Receptor in Human Tissue

Yamaura¹,

Suzuki²,

Namiki³

et al. 2012

Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment

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Section: Expression Of H 4 R In Human Skinsupporting

confidence: 68%

Section: Wwwintechopencommentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Effect Of H 4 R Antagonists On Pruritus Modelmentioning

confidence: 99%

See 2 more Smart Citations

Expression of the Histamine H4 Receptor in Human Tissue

Yamaura¹,

Suzuki²,

Namiki³

et al. 2012

Allergic Diseases - Highlights in the Clinic, Mechanisms and Treatment

Self Cite

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“…Moreover, it has been reported that H4 receptor agonists are able to induce itch through a direct action on the peripheral nerves (Bell et al, 2004), and that H4 antagonists inhibit SP-induced itch, which has been found to be resistant to H1 receptor antagonists (Yamaura et al, 2009). More recently, Suwa et al (2011) demonstrated that JNJ7777120 (10 and 30 mg·kg −1 day), but not the histamine H1 receptor antagonist fexofenadine (30 mg·kg −1 day), reduces the scratching behaviour and ameliorates the skin lesions induced by repeated challenge with 2,4,6-trinitrochlorobenzene in hairless mice, in a dose-dependent manner (Suwa et al, 2011).…”

Section: Histamine and Neurogenic Inflammation In The Skinmentioning

confidence: 99%

The role of histamine in neurogenic inflammation

Rosa

Fantozzi

2013

British J Pharmacology

167

138

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The term 'neurogenic inflammation' has been adopted to describe the local release of inflammatory mediators, such as substance P and calcitonin gene-related peptide, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established. The aim of this review is to summarize the most recent findings on the role of histamine in neurogenic inflammation, with particular regard to nociceptive pain, as well as neurogenic inflammation in the skin, airways and bladder. LINKED ARTICLESThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 Abbreviations CGRP, calcitonin gene-related peptide; ERs, oestrogen receptors; GERD, gastro-oesophageal reflux disease; HDC, histidine decarboxylase; IC, interstitial cystitis; PBS, painful bladder syndrome; SP, substance P; VIP, vasoactive intestinal peptide IntroductionThe term 'neurogenic inflammation' describes the local release of inflammatory mediators, such as substance P (SP) and calcitonin gene-related peptide (CGRP), from afferent neurons. The initial evidence for neurogenic vasodilatation in response to noxious stimuli was obtained in the skin of humans and other mammals (Schmelz and Petersen, 2001), but now it is recognized that neurogenic inflammation also occurs in visceral organs. The inflammatory response evoked by the activation of the sensory nerve fibres, which includes local vasodilatation, plasma extravasation, leukocyte and platelet adhesion, and mast cell degranulation, is brought about by neuropeptides released from the peripheral endings of sensory neurons upon stimulation of the primary sensory terminals. Both SP in neurons and histamine in mast cells have a dual mediator role in neurogenic inflammation (Figure 1). In fact, as demonstrated by Foreman and Jordan (1984), injury causes activation of sensory nerve endings either directly or through the release of histamine from the adjacent mast cells. The action potential generated travels orthodromically to the dorsal horn of the spinal cord and spreads to other branches of the same neurons, which will then release SP from their terminals or varicosities. The released SP, as well as contributing itself to local vasodilatation, induces histamine release from the adjacent mast cells, which produces flare and further activates other sensory nerve endings (Foreman et al., 1983).Neutrophils, whose responsiveness to SP has been repeatedly demonstrated, contribute to the inflammatory soup following neurogenic inflammation. In fact, neutrophils express the SP receptors NK 1, NK2 and NK3, and when stimulated with SP induce the expression of COX-2 and PGE2 release in the nanomolar range (Gallicchio et al., 2008;. Furthermore, SP at micromolar concentrations primes neutrophils, thus en...

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Clinical Development of Histamine H4 Receptor Antagonists

Thurmond

Venable

Savall

et al. 2017

Handbook of Experimental Pharmacology

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The discovery of the histamine H receptor (HR) provided a new avenue for the exploration of the physiological role of histamine, as well as providing a new drug target for the development of novel antihistamines. The first step in this process was the identification of selective antagonists to help unravel the pharmacology of the HR relative to other histamine receptors. The discovery of the selective HR antagonist JNJ 7777120 was vital for showing a role for the HR in inflammation and pruritus. While this compound has been very successful as a tool for understanding the function of the receptor, it has drawbacks, including a short in vivo half-life and hypoadrenocorticism toxicity in rats and dogs, that prevented advancing it into clinical studies. Further research let to the discovery of JNJ 39758979, which, similar to JNJ 7777120, was a potent and selective HR antagonist and showed anti-inflammatory and anti-pruritic activity preclinically. JNJ 39758979 advanced into human clinical studies and showed efficacy in reducing experimental pruritus and in patients with atopic dermatitis. However, development of this compound was terminated due to the occurrence of drug-induced agranulocytosis. This was overcome by developing another HR antagonist with a different chemical structure, toreforant, that does not appear to have this side effect. Toreforant has been tested in clinical studies in patients with rheumatoid arthritis, asthma, or psoriasis. In conclusions there have been many HR antagonists reported in the literature, but only a few have been studied in humans underscoring the difficulty in finding ligands with all of the properties necessary for testing in the clinic. Nevertheless, the clinical data to date suggests that HR antagonists can be beneficial in treating atopic dermatitis and pruritus.

show abstract

Histamine H4 receptor antagonist reduces dermal inflammation and pruritus in a hapten-induced experimental model

Cited by 42 publications

References 26 publications

Expression of the Histamine H4 Receptor in Human Tissue

Expression of the Histamine H4 Receptor in Human Tissue

The role of histamine in neurogenic inflammation

Clinical Development of Histamine H4 Receptor Antagonists

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