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Targeting adenosine receptors in the treatment of allergic rhinitis: a randomized, double-blind, placebo-controlled study

Authors


Correspondence:
Janet Rimmer, Woolcock Institute of Medical Research, Rhinitis Research Group, Blackburn Building D06, The University of Sydney, Room 461, Sydney, NSW 2006, Australia. E-mail: jrimmer@optusnet.com.au

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 A2A receptor agonist/adenosine A3 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 A2A and A3 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.

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