Details

Autor(en) / Beteiligte

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

Titel

Pharmacological Profiles of a Novel Tachykinin NK-2 Receptor Antagonist, TAC-363

Ist Teil von

• YAKUGAKU ZASSHI, 1996/11/25, Vol.116(11), pp.884-891

Ort / Verlag

Japan: The Pharmaceutical Society of Japan

Erscheinungsjahr

1996

Quelle

MEDLINE

Beschreibungen/Notizen

• We examined the pharmacological profiles of a novel tachykinin NK-2 receptor antagonist, Nα-(tert-butylcarbamoyl)-L-glutaminyl-L-tryptophyl-α-azaphenylalanine 2-benzyloxyethylamide (TAC-363). In vitro studies showed that TAC-363 caused a rightward shift of the contraction response curve with a slight inhibition of maximal response for the neurokin A (NKA)-induced contraction of the hamster trachea and parallel rightward shift of the curve for the substance P (SP)-induced contraction of the guinea-pig ileum. The pA2 values were 9.82 and 8.42 on the contraction by NKA and SP, respectively. The selectivity of TAC-363 to NK-2 receptor was 25 times higher than that to NK-1 receptor. The compound did not affect the histamine and acetylcholine-induced contraction of the guinea-pig ileum. Intravenous administration (0.1-1 mg/kg) of the compound inhibited dose-dependently both NKA-and capsaicin-induced bronchoconstriction in guinea-pigs. The inhibitory effect of the compound lasted up to 60 min on NKA-induced bronchoconstriction in guinea-pigs. These results suggest that TAC-363 is a potent and selective NK-2 receptor antagonist, which is effective in vitro and in vivo. It may be useful in the treatment of NKA-dependent pathology, especially bronchial asthma.