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


CONCLUSIONS
In conclusion, the tachykinin NK(2) receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma.
Schelfhout
Venessa
V
Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Van De Velde
Veerle
V
Maggi
Carlo
C
Pauwels
Romain
R
Joos
Guy
G
D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015288:Neurokinin A / Q000276:immunology; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D012129:Respiratory Function Tests; D055815:Young Adult
D001993:Bronchodilator Agents; C107754:MEN 11420; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; D015288:Neurokinin A