Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus

Dunford, Paul J.; Williams, Kacy N.; Desai, Pragnya J.; Karlsson, Lars; McQueen, Daniel S.; Thurmond, Robin L.

doi:10.1016/j.jaci.2006.08.034

Cited by 283 publications

(256 citation statements)

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“…Interestingly, in mice, blocking both the H1 receptors and the H4 receptors with a dual antagonist or a combination of drugs gave the maximum response; it almost completely abolished the itch response (Dunford et al, 2007).…”

Section: Histamine and Neurogenic Inflammation In The Skinmentioning

confidence: 99%

“…More recently, data obtained with clobenproprit, an H3 receptor antagonist and H4 receptor agonist, suggest that the H4 receptor is also involved in itch. Clobenproprit induced scratching responses in the mouse that were attenuated by pretreating the animals with the H4 receptor antagonist, JNJ7777120 (Dunford et al, 2007). 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) Interestingly, in mice, blocking both the H1 receptors and the H4 receptors with a dual antagonist or a combination of drugs gave the maximum response; it almost completely abolished the itch response (Dunford et al, 2007).…”

Section: Histamine and Neurogenic Inflammation In The Skinmentioning

confidence: 99%

“…Clobenproprit induced scratching responses in the mouse that were attenuated by pretreating the animals with the H4 receptor antagonist, JNJ7777120 (Dunford et al, 2007). 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) Interestingly, in mice, blocking both the H1 receptors and the H4 receptors with a dual antagonist or a combination of drugs gave the maximum response; it almost completely abolished the itch response (Dunford et al, 2007).In addition, other published data indicate that H1 and H4 receptors share a similar pathway, in that they stimulate neurons by increasing intracellular Ca 2+ levels (Shim and Oh, 2008). The histamine-induced increase in calcium levels is mediated through H1 receptors in rat cultured sensory neurons, and this effect is blocked by the PLC inhibitor U73122 (Nicolson et al, 2002).…”

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confidence: 99%

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The role of histamine in neurogenic inflammation

Rosa

Fantozzi

2013

British J Pharmacology

170

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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Section: Histamine and Neurogenic Inflammation In The Skinmentioning

confidence: 99%

Section: Histamine and Neurogenic Inflammation In The Skinmentioning

confidence: 99%

mentioning

confidence: 99%

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The role of histamine in neurogenic inflammation

Rosa

Fantozzi

2013

British J Pharmacology

170

138

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“…In atopic dermatitis, histamine may act as a pruritogen not only through H 1 receptors, but also through H 3 and H 4 receptors; in addition, cytokines such as interleukin-31 and other agents may be important pruritogens (Table 4B) [30-32]. …”

Section: Diseases In Which H1 Antihistamines Are Used But Are Not Drumentioning

confidence: 99%

“…Some of these medications might also have the intrinsic ability to down-regulate histamine at H 2 , H 3 , or H 4 receptors or to down-regulate leukotrienes or cytokines [2-4,32,53]. …”

Section: Summary and Future Directionsmentioning

confidence: 99%

H1 Antihistamines: Current Status and Future Directions

Simon

Simons

2008

World Allergy Organization Journal

102

107

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In this review, we compare and contrast the clinical pharmacology, efficacy, and safety of first-generation H1 antihistamines and second-generation H1 antihistamines. First-generation H1 antihistamines cross the blood-brain barrier, and in usual doses, they potentially cause sedation and impair cognitive function and psychomotor performance. These medications, some of which have been in use for more than 6 decades, have never been optimally investigated. Second-generation H1 antihistamines such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine cross the blood-brain barrier to a significantly smaller extent than their predecessors. The clinical pharmacology, efficacy, and safety of these medications have been extensively studied. They are therefore the H1 antihistamines of choice in the treatment of allergic rhinitis, allergic conjunctivitis, and urticaria. In the future, clinically advantageous H1 antihistamines developed with the aid of molecular techniques might be available.

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Allergy

Hodge

Sayers

2013

Encyclopedia of Life Sciences

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Allergy is an exaggerated, hypersensitive immune response to innocuous environmental antigens, characterised by inflammation and mediated by immunoglobulin E (IgE) antibodies. Symptoms of allergy depend on the site of allergen contact and range from being uncomfortable (itching, sneezing and breathlessness) to serious (anaphylaxis). The development of allergy is due to environmental and genetic factors; the heritable component is known as atopy, defined as a predisposition to the overproduction of IgE. The prevalence of allergies such as hay fever (seasonal allergic rhinitis), eczema (atopic dermatitis) and asthma are increasing in Westernised societies. Antihistamines are the first‐line drug treatment for allergy; however, these often fail to alleviate all symptoms satisfactorily and are not clinically effective in asthma, illustrating the heterogeneity of allergic disorders. This has necessitated the development of alternative medication for asthma, which targets airway symptoms, for example, β 2 ‐adrenergic receptor agonists. New, more effective therapeutic approaches are still required to treat allergic disease. Key Concepts: Allergy describes a variety of symptoms, which cause discomfort but can be life threatening. Allergic symptoms are a defining feature of diseases such as hay fever, eczema, asthma and food allergy. Atopy is a heritable trait (defined by elevated IgE or positive skin prick test), which predisposes an individual to allergic disease. Allergies are becoming increasingly common in Westernised societies and represent a significant economic burden, but the reasons for this are not fully understood. Recent improvements in technology have facilitated studies, which link genetic variants to atopy susceptibility, with confidence. New therapeutics are needed to more adequately treat symptoms of allergic diseases such as hay fever, eczema and asthma. Histamine is a key inflammatory mediator, the action of which might be targeted in new ways to treat the symptoms of allergic disease.

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Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus

Cited by 283 publications

References 42 publications

The role of histamine in neurogenic inflammation

The role of histamine in neurogenic inflammation

H1 Antihistamines: Current Status and Future Directions

Allergy

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