A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients.

Abstract

Recent reports suggest the involvement of vascular phenomena in exercise-induced asthma. Sensory neuropeptides, such as substance P (SP), which causes airway vascular dilatation and plasma leakage, have been demonstrated to play a role in hyperpnea-induced airway narrowing in animal studies. The purpose of this study was to investigate the importance of tachykinins in exercise-induced airway narrowing in patients with asthma using a selective neurokinin 1-receptor (NK1-receptor) antagonist, FK-888. In a double-blind, placebo-controlled, crossover trial, nine subjects with stable asthma were given FK-888 (2.5 mg) or placebo by inhalation 20 min before each exercise at a level previously demonstrated to cause a fall of at least 40% in specific airway conduction (SGaw). Inhalation of FK-888 had no significant effect on baseline SGaw. While the recovery from exercise-induced airway narrowing was significantly faster after treatment with FK-888 the area under the curve for SGaw during the 50 min after exercise was significantly reduced (p<0.05) and the time taken for the SGaw to recover to within 65% of baseline after exercise was also significantly shorter with FK-888 than the placebo (p<0.05). However, treatment with FK-888 did not significantly attenuate the maximal fall in SGaw. These results suggest that NK1-receptor-mediated mechanisms are involved in the recovery phase of exercise-induced airway narrowing. The possible mechanisms of these phenomena are discussed.

• Authors: M Ichinose, M Miura, H Yamauchi, N Kageyama, M Tomaki, T Oyake, Y Ohuchi, W Hida, H Miki, G Tamura, K Shirato
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 153 Issue 3 Pg. 936-41 (Mar 1996) ISSN: 1073-449X [Print] United States
• PMID: 8630576 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Dipeptides
• Indoles
• Neurokinin-1 Receptor Antagonists
• Tachykinins
• FK 888

Topics

• Administration, Inhalation
• Adolescent
• Adult
• Airway Resistance (drug effects)
• Asthma, Exercise-Induced (drug therapy)
• Bronchi (drug effects)
• Bronchial Spasm (drug therapy)
• Cross-Over Studies
• Dipeptides (therapeutic use)
• Double-Blind Method
• Exercise Test
• Female
• Humans
• Indoles (therapeutic use)
• Male
• Middle Aged
• Neurokinin-1 Receptor Antagonists
• Tachykinins (antagonists & inhibitors)