Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients.

Abstract

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 (3.3x10(-9) to 1.0x10(-6) mol x mLP(-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 x mL(-1) at 1 h after DNK333 treatment and -6.8 log10 mol x 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.

• Authors: G F Joos, W Vincken, R Louis, V J Schelfhout, J H Wang, M J Shaw, G D Cioppa, R A Pauwels
• Journal: The European respiratory journal (Eur Respir J) Vol. 23 Issue 1 Pg. 76-81 (Jan 2004) ISSN: 0903-1936 [Print] England
• PMID: 14738235 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Aza Compounds
• Benzamides
• DNK 333
• Receptors, Tachykinin
• Neurokinin A

Topics

• Administration, Inhalation
• Adolescent
• Adult
• Asthma (physiopathology)
• Aza Compounds (administration & dosage, pharmacokinetics, pharmacology)
• Benzamides (administration & dosage, pharmacokinetics, pharmacology)
• Bronchoconstriction (drug effects)
• Cross-Over Studies
• Double-Blind Method
• Humans
• Middle Aged
• Neurokinin A (administration & dosage, adverse effects)
• Receptors, Tachykinin (antagonists & inhibitors)