PT  - JOURNAL ARTICLE
AU  - G.F. Joos
AU  - W. Vincken
AU  - R. Louis
AU  - V.J. Schelfhout
AU  - J.H. Wang
AU  - M.J. Shaw
AU  - G.D. Cioppa
AU  - R.A. Pauwels
TI  - Dual tachykinin NK<sub>1</sub>/NK<sub>2</sub> antagonist DNK333 inhibits neurokinin A‐induced bronchoconstriction in asthma patients
AID  - 10.1183/09031936.03.00101902
DP  - 2004 Jan 01
TA  - European Respiratory Journal
PG  - 76--81
VI  - 23
IP  - 1
4099  - http://erj.ersjournals.com/content/23/1/76.short
4100  - http://erj.ersjournals.com/content/23/1/76.full
SO  - Eur Respir J2004 Jan 01; 23
AB  - Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma. In vitro both tachykinin NK1 and NK2 receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2 receptor antagonist, DNK333, on NKA‐induced bronchoconstriction in asthma. A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled, crossover trial. Increasing concentrations of NKA (3.3×10−9 to 1.0×10−6 mol·mL−1) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo. It was observed that DNK333 did not affect baseline lung function but did protect against NKA‐induced bronchoconstriction in those patients. The mean log10 provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was −5.6 log10 mol·mL−1 at 1 h after DNK333 treatment and −6.8 log10 mol·mL−1 after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment. The results shown in this report indicate that DNK333 blocks neurokinin A‐induced bronchoconstriction in patients with asthma. This project was supported by a grant from Novartis, Belgium. Part of this paper was presented at the American Thoracic Society International Conference in May 2001, San Francisco, California.