YM158 free base  (Synonyms: YM-57158)

YM158 free base is a potent and selective LTD₄ and TXA₂ receptor antagonist with pA₂ values of about 8.87 and 8.81, respectively.

YM158 antagonizes leukotriene (LT) D₄ and thromboxane (TX) A₂ receptors. Functional assays in vitro show 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 is approximately 6.5 times less potent than that of Montelukast, and that for the TXA₂ receptor is 2.5 times more potent than that of Seratrodast. YM158 also inhibits PGD₂- and PGF_2α -induced tracheal contractions. YM158 antagonizes the stable TXA₂ analog U46619-induced aggregation of both guinea pig and human platelets and inhibits the LTD₄-induced contraction of guinea pig ileum. YM158 produces a concentration-dependent inhibition of guinea pig ileum contraction induced by 1 nM LTD₄ with an IC₅₀ value of 0.58 nM^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

YM158, an orally active dual antagonist for LTD₄ and TXA₂ receptors, is expected to have a stronger antiasthmatic efficacy in a broader class of asthmatic patients than single antagonistic drugs.The effect of YM158 is examined on these asthmatic responses in mediator-controlled and passively sensitized guinea pigs. Because the inhibitory effects of YM158 on increase in the airway resistance induced by LTD₄ or U46619 are shown to be dose-dependent when p.o. administered 1 h before LTD₄ or U46619 injection, with ED₅₀ values of 8.6 and 14 mg/kg, respectively, the antagonistic activities of p.o. YM158 for LTD₄ and TXA₂ receptors are exhibited at the same dose range. Oral YM158 shows significant effects, approximately the same as the combination of Pranlukast and Daltroban on antigen-induced response under various conditions; namely, where LTD₄ is predominant, TXA₂ is predominant; or where both mediators participated equally. In groups not treated with Indomethacin, administration of Daltroban (10 mg/kg), a combination of Pranlukast (30 mg/kg) and Daltroban (10 mg/kg), or YM158 (30 mg/kg) significantly prolongs the onset time for asthmatic response and significantly suppresses symptoms^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

681.22

C₃₂H₃₃ClN₆O₅S₂

179102-65-9

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Arakida Y, et al. In vitro pharmacologic profile of YM158, a new dual antagonist for LTD₄ and TXA₂ receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.  [Content Brief]

  [2]. Arakida Y, et al. Effects of lipid mediator antagonists on predominant mediator-controlled asthmatic reactions in passively sensitized guinea pigs. J Pharmacol Exp Ther. 1999 Sep;290(3):1285-91.  [Content Brief]