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