Histamine receptors that influence blockage of the normal human nasal airway

Abstract

The aim of this study was to investigate the mechanisms by which histamine causes nasal blockage. Histamine, 40–800 μg, intranasally into each nostril, induced significant blockage of the nasal airway in normal human subjects, as measured by acoustic rhinometry. Oral pretreatment with cetirizine, 5–30 mg, the H1 antagonist, failed to reverse completely the nasal blockage induced by histamine, 400 μg. Dimaprit, 50–200 μg, the H2 agonist, intranasally, caused nasal blockage, which was reversed by oral pretreatment with ranitidine, 75 mg, the H2 antagonist. A combination of cetirizine, 20 mg, and ranitidine, 75 mg, caused greater inhibition of the nasal blockage caused by histamine, 400 μg, than cetirizine alone. In the presence of both antagonists, there was residual histamine‐induced nasal blockage. R‐α‐methylhistamine (R‐α‐MeH), 100–600 μg, the H3 agonist, intranasally, caused nasal blockage, which was not inhibited by either cetirizine or ranitidine. Thioperamide, 700 μg, the H3 antagonist, intranasally, reversed the R‐α‐MeH‐induced nasal blockage. Thioperamide alone had no significant action on the nasal blockage induced by histamine, 400 and 1000 μg, but, in the presence of cetirizine, 20 mg, thioperamide further reduced the histamine‐induced nasal blockage. Corynanthine, 2 mg, the α1‐adrenoceptor antagonist, administered intranasally, caused nasal blockage. Corynanthine produced a greater increase in nasal blockage when in combination with bradykinin compared to its combination with R‐α‐MeH. There appears to be a contribution of H1, H2 and H3 receptors to histamine‐induced nasal blockage in normal human subjects. The sympathetic nervous system actively maintains nasal patency and we suggest that activation of nasal H3 receptors may downregulate sympathetic activity. British Journal of Pharmacology (2005) 144, 867–874. doi:10.1038/sj.bjp.0706118

The effects of an H3 receptor antagonist (PF-03654746) with fexofenadine on reducing allergic rhinitis symptoms

“…8 In healthy human subjects the nasal congestive effect of an intranasal H 3 receptor agonist was inhibited by intranasal delivery of the H 3 /H 4 receptor antagonist thioperamide. 9 Optimally, a novel acute treatment for allergic rhinitis would treat all symptoms associated with the condition. As such, it is envisaged that H 3 receptor antagonists will be developed as combination agents with established H 1 receptor antagonists, given that H 3 receptor antagonists might provide decongestant efficacy in concert with the effects of H 1 receptor antagonists on sneezing, itching, and rhinorrhea.…”

The Efficacy and Tolerability of Two Novel H₁/H₃ Receptor Antagonists in Seasonal Allergic Rhinitis

“…Thioperamide, an H 3 antagonist had no significant action on the nasal blockage induced by histamine when given alone, but in the presence of the H 1 antagonist cetirizine, thioperamide reduced the histamine-induced nasal blockage above that seen with cetirizine alone [20]. Administration of a specific H 3 agonist to the nasal airways also induced nasal blockage which was reversed by the addition of thioperamide, so there appears to be a contribution of H 3 receptors to histamine-induced nasal blockage in normal human subjects [20]. Activation of H 3 receptors in isolated human nasal turbinate mucosa was also shown to inhibit sympathetic vasoconstriction [21].…”

“…It was proposed that these novel H 1 /H 3 antagonists, known as GSK1004723 and GSK835726, would offer a breakthrough in allergic rhinitis, since they would not only provide relief from the symptoms which are attenuated by H 1 receptor blockade such as rhinorrhoea, sneezing and itching, but would also provide relief from nasal congestion through H 3 receptor antagonism resulting in enhanced sympathetically mediated nasal vascular constriction [20,21]. There is limited published clinical data for such compounds in allergic rhinitis, although data for one such compound has been published [23].…”

Concomitant Activity of Histamine and Cysteinyl Leukotrienes on Porcine Nasal Mucosal Vessels and Nasal Inflammation in the Rat

“…Since the early 1900s, scientific evidence has amassed implicating the involvement of mast cell histamine in the elicitation of allergic rhinitis symptoms [7,8] . For example: (1) histamine is released after allergen exposure [9][10][11] ; (2) the level of histamine in nasal lavage fluid correlates with allergic nasal symptoms [12] ; (3) topical nasal application of histamine induces sneezing and a decrease in nasal patency, effectively mimicking these symptoms of allergic rhinitis [13] , and finally, (4) antihistamines (histamine H 1 receptor antagonists) alleviate many allergic rhinitis symptoms.…”