The NK-2 receptor antagonist SR 48968C does not improve adenosine hyperresponsiveness and airway obstruction in allergic asthma

Authors


Dr J. Kraan, Department of Pulmonology, University Hospital Groningen, Postbox 30.001, 9700 RB Groningen, The Netherlands. E-mail: j.kraan@int.azg.nl

Abstract

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.

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.

SR 48968C had no significant effect on PC20AMP 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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