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Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double‐blind, placebo‐controlled study
Author(s) -
Rimmer J.,
Peake H. L.,
Santos C. M.C.,
Lean M.,
Bardin P.,
Robson R.,
Haumann B.,
Loehrer F.,
Handel M. L.
Publication year - 2007
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2006.02546.x
Subject(s) - medicine , nasal administration , tryptase , pharmacology , house dust mite , immunology , nasal provocation test , placebo , adenosine receptor , agonist , allergy , receptor , allergen , mast cell , pathology , alternative medicine
Summary Background There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases. Objective The study evaluated the efficacy of intranasal treatment with an adenosine A 2A receptor agonist/adenosine A 3 receptor antagonist (50 μg), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice‐daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. Methods A randomized, double‐blind, double‐dummy, placebo‐controlled, three‐way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus , rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil‐activating protein‐78 (ENA‐78), IL‐5 and IL‐8 in nasal secretions were measured and treatment groups were compared. Results Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators. Conclusion A novel agonist/antagonist of adenosine A 2A and A 3 receptors appears to have limited clinical benefit in both the early‐phase and the late‐phase response to intranasal allergen challenge. However, reduction of some pro‐inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.