The effect of the tachykinin NK(2) receptor antagonist MEN11420 (nepadutant) on neurokinin A-induced bronchoconstriction in asthmatics.

Abstract

OBJECTIVE:

We previously reported that the nonpeptide tachykinin NK(2) receptor antagonist SR48968 (saredutant) significantly inhibits neurokinin A-induced bronchoconstriction in patients with asthma. MEN11420 (nepadutant) is a bicyclic peptide tachykinin NK(2) receptor antagonist. The aim of the trial was to examine the effect of nepadutant on neurokinin A-induced bronchoconstriction in man.

METHODS:

12 patients with stable, mild to moderate asthma participated in a double-blind, placebo-controlled crossover trial and received, with intervals of 1 week, MEN11420 2 mg, MEN11420 8 mg and placebo (i.v.). Increasing concentrations of NKA (10(-9) to 10(-6) moles/ml) were inhaled immediately after (d1) and 24 hours after (d2) administration of treatment.

RESULTS:

On d1 both MEN11420 2 and 8 mg shifted the dose response curve for neurokinin A to the right (log PC(20) FEV(1) neurokinin A [moles/ml]; mean + or = or - SEM -6.38 + or - 0.26 after 2 mg, -6.11 + or - 0.23 after 8 mg, versus -6.95 + or - 0.27 after placebo]. On d2 MEN11420 had no effect on neurokinin A-induced bronchoconstriction.

CONCLUSION:

In conclusion, the tachykinin NK(2) receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma.

• Authors: Venessa Schelfhout, Veerle Van De Velde, Carlo Maggi, Romain Pauwels, Guy Joos
• Journal: Therapeutic advances in respiratory disease (Ther Adv Respir Dis) Vol. 3 Issue 5 Pg. 219-26 (Oct 2009) ISSN: 1753-4666 [Electronic] England
• PMID: 19880429 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bronchodilator Agents
• MEN 11420
• Peptides, Cyclic
• Receptors, Neurokinin-2
• Neurokinin A

Topics

• Adult
• Asthma (drug therapy)
• Bronchial Provocation Tests
• Bronchoconstriction (drug effects, immunology)
• Bronchodilator Agents (therapeutic use)
• Cross-Over Studies
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Neurokinin A (immunology)
• Peptides, Cyclic (therapeutic use)
• Receptors, Neurokinin-2 (antagonists & inhibitors)
• Respiratory Function Tests
• Young Adult