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


CONCLUSIONS
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.
Rimmer
J
J
Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia. jrimmer@optusnet.com.au
Peake
H L
HL
Santos
C M C
CM
Lean
M
M
Bardin
P
P
Robson
R
R
Haumann
B
B
Loehrer
F
F
Handel
M L
ML
D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000485:Allergens; D000730:Androstadienes / Q000627:therapeutic use; D000818:Animals; D018926:Anti-Allergic Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001623:Betamethasone / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068298:Fluticasone; D006801:Humans; D015848:Interleukin-5 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry; D009299:Nasal Provocation Tests; D010919:Placebos; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D053802:Tryptases / Q000032:analysis
C522066:(2R,3R,4S,5R)-2-(6-amino-2-(((1S)-2-hydroxy-1-(phenylmethyl)ethyl)amino)-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3,4-furandiol; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000485:Allergens; D000730:Androstadienes; D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D015848:Interleukin-5; D016209:Interleukin-8; D010919:Placebos; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D013777:Tetrazoles; D001623:Betamethasone; D000068298:Fluticasone; D053802:Tryptases