Details

Autor(en) / Beteiligte

• HIGASHIDE, Yasushi
• YATABE, Yoriko
• ARAI, Yoko
• SHIBATA, Masahiro
• YAMAURA, Tetsuaki

Titel

Effect of a novel tachykinin NK-2-receptor antagonist, TAC-363, on bronchoconstriction and airway hyperresponsiveness in guinea pigs

Ist Teil von

• Folia Pharmacologica Japonica, 1997, Vol.109(1), pp.19-29

Ort / Verlag

Japan: The Japanese Pharmacological Society

Erscheinungsjahr

1997

Quelle

MEDLINE

Beschreibungen/Notizen

• We examined the effect of a novel tachykinin NK-2-receptor antagonist, Nα-(tert-Butylcarbamoyl)-L-glutaminyl-L-tryptophyl-α-aza-phenylalanine 2-benzyloxyethylamide (TAC-363), on hyperventilation- and citric acid-induced bronchoconstriction and neurokinin A (NKA)-, capsaicin- and antigen-induced airway hyperresponsiveness in guinea pigs. The i.v. administration of TAC-363 at doses of 0.01-1 mg/kg inhibited hyperventilation- and citric acid-induced bronchoconstriction in a dose-dependent manner, while FK-888, a tachykinin NK-1-receptor antagonist, did not inhibit hyperventilation-induced bronchoconstriction. NKA-induced airway hyperresponsiveness to acetylcholine was attenuated by i.v. injection of TAC-363, but not by the thromboxane A2 synthetase inhibitor ozagrel and the mast cell stabilizer DSCG. Furthermore, TAC-363 prevented the occurrence of capsaicin- and antigen-induced airway hyperresponsiveness to acetylcholine, while FK-888 did not prevent occurrence of capsaicin-induced airway hyperresponsiveness. In summary, TAC-363 inhibits bronchoconstriction and airway hyperresponsiveness induced by various stimuli. These results suggest that NKA mediates bronchoconstriction and airway hyperresponsiveness. Thus, TAC-363 is expected to be useful in the treatment of airway diseases such as asthma.