Reference : Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstr...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients
Joos, G. F. [> > > >]
Vincken, W. [> > > >]
Louis, Renaud mailto [Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie]
Schelfhout, V. J. [> > > >]
Wang, J. H. [> > > >]
Shaw, M. J. [> > > >]
Cioppa, G. D. [> > > >]
Pauwels, R. A. [> > > >]
European Respiratory Journal
Yes (verified by ORBi)
[en] asthma ; bronchoconstriction ; DNK333 ; neurokinin A ; substance P ; tachykinins
[en] 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 x 10(-9) to 1.0 x 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 log(10) provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was -5.6 log(10) mol(.)mL(-1) at 1 h after DNK333 treatment and -6.8 log(10) 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.

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