Document Detail

Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients.
MedLine Citation:
PMID:  14738235     Owner:  NLM     Status:  MEDLINE    
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.
G F Joos; W Vincken; R Louis; V J Schelfhout; J H Wang; M J Shaw; G D Cioppa; R A Pauwels
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The European respiratory journal     Volume:  23     ISSN:  0903-1936     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-23     Completed Date:  2004-04-27     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  76-81     Citation Subset:  IM    
Dept of Respiratory Diseases, Ghent University Hospital, Belgium.
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MeSH Terms
Administration, Inhalation
Asthma / physiopathology*
Aza Compounds / administration & dosage,  pharmacokinetics,  pharmacology*
Benzamides / administration & dosage,  pharmacokinetics,  pharmacology*
Bronchoconstriction / drug effects*
Cross-Over Studies
Double-Blind Method
Middle Aged
Neurokinin A / administration & dosage,  adverse effects*
Receptors, Tachykinin / antagonists & inhibitors*
Reg. No./Substance:
0/Aza Compounds; 0/Benzamides; 0/DNK 333; 0/Receptors, Tachykinin; 86933-74-6/Neurokinin A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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