The triple neurokinin-receptor antagonist CS-003 inhibits neurokinin A-induced bronchoconstriction in patients with asthma.

Abstract

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 24 h 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 1h post-dose and in 5/16 patients at 8 h 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 8h post-dose in mild asthmatics.

• Authors: V Schelfhout, R Louis, W Lenz, R Heyrman, R Pauwels, G Joos
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 19 Issue 6 Pg. 413-8 ( 2006) ISSN: 1094-5539 [Print] England
• PMID: 16364669 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Neurokinin-1 Receptor Antagonists
• Receptors, Neurokinin-2
• Receptors, Neurokinin-3
• Neurokinin A

Topics

• Adolescent
• Adult
• Asthma (physiopathology)
• Bronchial Provocation Tests
• Bronchoconstriction (drug effects)
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Forced Expiratory Volume
• Humans
• Male
• Middle Aged
• Neurokinin A (antagonists & inhibitors, pharmacology)
• Neurokinin-1 Receptor Antagonists
• Receptors, Neurokinin-2 (antagonists & inhibitors)
• Receptors, Neurokinin-3 (drug effects)
• Reproducibility of Results
• Respiratory Function Tests