{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:18:21Z","timestamp":1772792301131,"version":"3.50.1"},"reference-count":0,"publisher":"European Respiratory Society (ERS)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"published-print":{"date-parts":[[1998,7,1]]},"abstract":"<jats:p>Inhalation of neurokinin (NK) A causes bronchoconstriction in patients with asthma. The NKA-induced bronchoconstriction in isolated human airways is mediated via the NK2 receptor and inhibited by SR 48968, a potent and specific nonpeptide tachykinin NK2 receptor antagonist. In the present study, the effect of orally administered SR 48968 on NKA-induced bronchoconstriction was examined in 12 mild asthmatics. On the screening day and during the study periods, increasing concentrations of NKA (3.3 x 10(-9) to 1.0 x 10(-6) mol x mL(-1)) were inhaled, until the forced expiratory volume in one second (FEV1) and specific airway conductance (sGaw) decreased by at least 20 and 50%, respectively. During the study periods, 100 mg SR 48968 or matched placebo was ingested in a double-blind, randomized, crossover fashion and NKA provocation was performed at 1.5 and 24 h after dosing. At 1.5 h, the mean (SEM) log10 provocative concentration of NKA causing a 20% fall in FEV1 (PC20 FEV1) was -6.25 (0.20) after SR 48968 and -6.75 (0.17) after placebo (p=0.05); the mean log10 provocative concentration of NKA causing a 35% fall in sGaw (PC35 sGaw) was -7.02 (0.28) after SR 48968 and -7.64 (0.19) after placebo (p=0.05). At 24 h, the mean log10 PC20 FEV1 was -6.21 (0.17) after SR 48968 and -6.65 (0.11) after placebo (p=0.05); the mean log10 PC35 sGaw was -6.85 (0.23) after SR 48968 and -7.17 (0.15) after placebo (nonsignificant). As PC20 FEV1 and\/or PC35 sGaw were not reached in up to 4 patients per SR 48968 group, the differences between SR 48968 and placebo were underestimated. In conclusion, oral treatment with 100 mg SR 48968 caused a significant inhibition of neurokinin A-induced bronchoconstriction in asthmatics. This finding constitutes the first evidence of inhibition of sensory neuropeptide-induced bronchoconstriction by a selective tachykinin receptor antagonist in humans.<\/jats:p>","DOI":"10.1183\/09031936.98.12010017","type":"journal-article","created":{"date-parts":[[2002,11,14]],"date-time":"2002-11-14T00:39:00Z","timestamp":1037234340000},"page":"17-23","source":"Crossref","is-referenced-by-count":82,"title":["The effect of the NK2 tachykinin receptor antagonist SR 48968 (saredutant) on neurokinin A-induced bronchoconstriction in asthmatics"],"prefix":"10.1183","volume":"12","author":[{"given":"J","family":"Van Schoor","sequence":"first","affiliation":[]},{"given":"GF","family":"Joos","sequence":"additional","affiliation":[]},{"given":"BL","family":"Chasson","sequence":"additional","affiliation":[]},{"given":"RJ","family":"Brouard","sequence":"additional","affiliation":[]},{"given":"RA","family":"Pauwels","sequence":"additional","affiliation":[]}],"member":"81","published-online":{"date-parts":[[1998,7,1]]},"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/09031936.98.12010017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T07:09:54Z","timestamp":1740380994000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/09031936.98.12010017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,7,1]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[1998,7,1]]},"published-print":{"date-parts":[[1998,7,1]]}},"alternative-id":["10.1183\/09031936.98.12010017"],"URL":"https:\/\/doi.org\/10.1183\/09031936.98.12010017","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,7,1]]}}}