The effect of selective antagonist of H4 receptor JNJ7777120 on nasal symptoms, cough, airway reactivity and inflammation in guinea pigs

• Allergic rhinitis induced in experimental conditions up-regulates coughing and airway responsiveness via inflammation and neural mechanisms.
• JNJ7777120–novel histamine H4 receptor antagonist reduces nasal symptoms, number of coughs and airway inflammation.
• JNJ7777120 also reduces airway responsiveness measured in vitro and in vivo.
• H4 receptor antagonists are promising class of drugs with potential clinical application in subjects with upper airway diseases and/or cough.

The efficacy of H4R antagonist JNJ7777120 on nasal symptoms, cough, airway resistance (Raw), inflammatory cell count in bronchoalveolar lavage (BAL) and blood in ovalbumin (OVA) induced allergic rhinitis (AR) was studied in guinea pigs. Animals (n = 8) were sensitized by i.p. OVA and were repeatedly challenged with nasal OVA to induce rhinitis, seven animals were not sensitized. Animals were pre-treated with JNJ7777120 2.5 and 5 mg/kg i.p. 30 min prior OVA. Cough was induced by inhalation of citric acid, Raw was measured in vivo by Pennock's method as baseline, during AR and after JNJ7777120 treatment. Leucocyte count in BAL and blood was analyzed. JNJ7777120 (5 mg/kg) significantly suppressed nasal symptoms and the number of coughs. This compound significantly inhibited airway reactivity to histamine, but not methacholine. Pre-treatment with JNJ7777120 5 mg/kg did not influence significantly the leucocyte count in BAL and blood except for a significant decrease in monocyte count in blood compared to the control group (p < 0.05). We conclude that the antitussive action of JNJ7777120 is peripheral. The primary effect of the compound is anti-inflammatory, and the suppression of cough is a consequence of reduced airway inflammation.