The effect of the tachykinin NK2 receptor antagonist MEN11420 (nepadutant) on neurokinin A-induced bronchoconstriction in asthmatics

Abstract

Objective: We previously reported that the nonpeptide tachykinin NK2 receptor antagonist SR48968 (saredutant) significantly inhibits neurokinin A-induced bronchoconstriction in patients with asthma. MEN11420 (nepadutant) is a bicyclic peptide tachykinin NK2 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 PC20 FEV1 neurokinin A [moles/ml]; mean± SEM -6.38±0.26 after 2 mg-6.11±0.23 after 8 mg, versus -6.95±0.27 after placebo]. On d2 MEN11420 had no effect on neurokinin A-induced bronchoconstriction. Conclusion: In conclusion, the tachykinin NK2 receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma. © 2009, SAGE Publications. All rights reserved.