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

Venessa Schelfhout

Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

Veerle Van De Velde

Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

Carlo Maggi

Menarini Ricerce, Florence, Italy

Romain Pauwels

Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

Guy Joos

Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium guy.joos{at}Ugent.be

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.

Key Words: asthma • tachykinins • neurokinin A • bronchoconstriction • NK2 receptor antagonist

Therapeutic Advances in Respiratory Disease, Vol. 3, No. 5, 219-226 (2009)
DOI: 10.1177/1753465809349741
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