A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients.
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.
Ichinose
M
M
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Miura
M
M
Yamauchi
H
H
Kageyama
N
N
Tomaki
M
M
Oyake
T
T
Ohuchi
Y
Y
Hida
W
W
Miki
H
H
Tamura
G
G
Shirato
K
K
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001250:Asthma, Exercise-Induced / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects; D001986:Bronchial Spasm / Q000188:drug therapy; D018592:Cross-Over Studies; D004151:Dipeptides / Q000627:therapeutic use*; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D064729:Neurokinin-1 Receptor Antagonists; D015320:Tachykinins / Q000037:antagonists & inhibitors
D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D015320:Tachykinins; C078949:FK 888