[en] Neurokinin A (NKA) causes bronchoconstriction in asthmatic patients. In vitro both NK1 and NK2 receptors can mediate airway contraction. Moreover in guinea pigs, NK3 receptors facilitate cholinergic neurotransmission. Dual tachykinin NK1/NK2 receptor antagonism results in prevention of NKA-induced bronchoconstriction. We have now examined the effect of a single dose of the triple tachykinin receptor antagonist CS-003 on NKA-induced bronchoconstriction in asthmatics. A double blind, crossover, placebo-controlled trial in 16 mild asthmatics was performed. One single dose of CS-003 (200 mg, solution in distilled water) or matched placebo was given orally on the assessment days. NKA-provocation tests were performed pre-dose and 1, 8 and 24h after dosing. There was a significant shift to the right of the dose-response curve at 1 and 8 h after intake of CS-003. PC20 was not reached in 12/16 patients at 1 h post-dose and in 5/16 patients at 8h post-dose. This did not occur under placebo treatment. A single dose of 200 mg CS-003 protected significantly against NKA-induced bronchoconstriction at 1 and 8 h post-dose in mild asthmatics. (c) 2005 Elsevier Ltd. All rights reserved.
Disciplines :
Cardiovascular & respiratory systems Pharmacy, pharmacology & toxicology
Author, co-author :
Schelfhout, V.
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Lenz, W.
Heyman, R.
Pauwels, R.
Joos, G.
Language :
English
Title :
The triple neurokinin-receptor antagonist CS-003 inhibits neurokinin A-induced bronchoconstriction in patients with asthma
Publication date :
2006
Journal title :
Pulmonary Pharmacology and Therapeutics
ISSN :
1094-5539
eISSN :
1522-9629
Publisher :
Academic Press Ltd Elsevier Science Ltd, London, United Kingdom
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