EFFECT OF AN NK1 RECEPTOR ANTAGONIST (CP-99,994) ON HYPERTONIC SALINE-INDUCED BRONCHOCONSTRICTION AND COUGH IN MALE ASTHMATIC SUBJECTS

To investigate the role of NK1 receptors in the pathogenesis of bronch oconstriction and cough in asthma, we performed a randomized, double-b lind, crossover study on the effects of a selective nonpeptide tachyki nin NK1 receptor antagonist (CP-99,994) on baseline measures of lung f unction and on hypertonic saline-induced bronchoconstriction and cough in 14 male subjects with mild asthma. CP-99,994 (250 mu g/2 hours) an d placebo were administered intravenously in 2-h infusions during cons ecutive visits 5 to 7 d apart. Specific airway resistance (SRaw) was m easured and spirometry was performed at baseline and at 35 and 60 min. Next, hypertonic saline challenge was performed by delivering 10 brea ths of saline of increasing concentration (0.9 to 7% in 1% increments at 5-min intervals) via an ultrasonic nebulizer until SRaw increased f rom baseline by 200% or 20 units, whichever was greater, Throughout th e challenge cough was counted from a taped record made from two microp hones placed close to the subject's larynx. We found that CP-99,994 di d not significantly affect SRaw or spirometric measures of lung functi on during the first hour of infusion. Although CP-99,994 infusion mark edly attenuated the bronchoconstrictor response to the saline challeng e in two subjects, it did not significantly decrease the area under cu rves obtained for SRaw and cough during saline challenge for the group as a whole (p = 0.9 for SRaw; p = 0.8 for cough). We conclude that ad ministration of 250 mu g/kg of CP-99,994 over 2 h does not significant ly inhibit hypertonic saline-induced bronchoconstriction or cough in s ubjects with mild asthma and does not have acute bronchodilator activi ty in these subjects.