期刊
CLINICAL AND EXPERIMENTAL ALLERGY
卷 31, 期 2, 页码 274-278出版社
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1365-2222.2001.00975.x
关键词
asthma; adenosine hyperresponsiveness; neurokinins; NK-2 receptor antagonist; SR 48968C
Background When stimulated, excitatory nonadrenergic noncholinergic (e-NANC) nerves locally release tachykinins like Neurokinin (NK) A and Substance P, causing neurogenic inflammation and airway obstruction via activation of specific NK-1 and NK-2 receptors. The recently developed nonpeptide NK-2 receptor antagonist SR 48968C has a high affinity for the NK-2 receptor, and is a strong and selective antagonist of NK-2 receptor mediated airway obstruction. Objective and methods in a placebo-controlled cross-over study, we investigated the effect of SR 48968C, administrated orally once-daily in a dosage of 100 mg during 9 days, on airway responsiveness to adenosine 5'-monophosphate (AMP) in 12 allergic asthmatic patients. Furthermore, we assessed its effect on airway obstruction, by measuring FEV1 on the first and last day of each treatment period and by peak flow registration at home throughout the study period. Results and conclusion SR 48968C had no significant effect on PC(20)AMP or on FEV1 measured on day 1 and 9, and morning and evening peakflow measured at home on day 2-8. Thus, although SR 48968C was administrated in a dosage that might cause a demonstrable blocking effect on airway NK-2 receptors in asthma, it did not have a significant bronchodilatory or bronchoprotective effect against adenosine hyperresponsiveness in this study. Further studies are needed to assess the value of SR 48968C and other NK receptor antagonists in the treatment of asthma.
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