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

Abstract

We examined the effect of a novel tachykinin NK-2-receptor antagonist, N alpha-(tert-Butylcarbamoyl)-L-glutaminyl-L-tryptophyl-alpha-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.

• Authors: Y Higashide, Y Yatabe, Y Arai, M Shibata, T Yamaura
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 109 Issue 1 Pg. 19-29 (Jan 1997) ISSN: 0015-5691 [Print] Japan
• PMID: 9067996 (Publication Type: English Abstract, Journal Article)

Chemical References

• Oligopeptides
• Receptors, Tachykinin
• TAC 363
• Tachykinins
• Citric Acid
• Neurokinin A
• Capsaicin

Topics

• Animals
• Bronchoconstriction (drug effects)
• Capsaicin (pharmacology)
• Citric Acid (pharmacology)
• Guinea Pigs
• Hyperventilation (physiopathology)
• Male
• Neurokinin A (pharmacology)
• Oligopeptides (pharmacology)
• Receptors, Tachykinin (antagonists & inhibitors)
• Respiratory Hypersensitivity (prevention & control)
• Tachykinins (antagonists & inhibitors)