RT Journal Article
SR Electronic
T1 <em>In Vitro</em> Pharmacologic Profile of YM158, a New Dual Antagonist for LTD<sub>4</sub> and TXA<sub>2</sub> receptors
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 633
OP 639
VO 287
IS 2
A1 Yasuhito Arakida
A1 Kiyomi Suwa
A1 Keiko Ohga
A1 Masaki Yokota
A1 Keiji Miyata
A1 Toshimitsu Yamada
A1 Kazuo Honda
YR 1998
UL http://jpet.aspetjournals.org/content/287/2/633.abstract
AB YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5′-[3-(4-chlorobenzenesulfonyl) propyl]-2′-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate) antagonizes leukotriene (LT) D4 and thromboxane (TX) A2 receptors. Functional assays in vitro showed that YM158 exhibits competitive dual antagonism of LTD4 and TXA2 receptor-mediated contraction of isolated guinea pig tracheae, with pA2 values of about 8.87 and 8.81, respectively. Its antagonistic activity for the LTD4 receptor was approximately 6.5 times less potent than that of montelukast, and that for the TXA2 receptor was 2.5 times more potent than that of seratrodast. YM158 also inhibited PGD2- and PGF2α-induced tracheal contractions. YM158 showed no antagonism against LTC4-, histamine- or carbachol-induced contractions of guinea pig tracheae. Furthermore, YM158 antagonized the stable TXA2 analog U46619-induced aggregation of both guinea pig and human platelets and inhibited the LTD4-induced contraction of guinea pig ileum. From these results, YM158 appears to be a novel, selective dual antagonist for both LTD4 and TXA2 receptors. The American Society for Pharmacology and Experimental Therapeutics