Introduction of 115104-28-4 :
MK-571 is a potent, selective, orally active leukotriene receptor antagonist, which inhibits [3H] LTD4 binding in guinea pig lung with a Ki of 0.22±0.15 nM and [3H]LTD4 binding in human lung with a Ki of 2.1±1.8 nM. IC50 & Target: Ki: 0.22±0.15 nM (LTD4, in guinea pig lung), 2.1±1.8 nM (LTD4, in human lung)[1] In Vitro: MK-571 (L660,711) is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes. MK-571 is essentially inactive versus [3H]LTC4 binding with IC50 values of 23±11 μM (n=16) and 32 μM (n=1) in guinea pig and human lung, respectively. MK-571 competitively antagonizes contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). MK-571 (58 nM) antagonizes contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio=28) but not in the presence of 45 mM L-serine borate (dose ratio less than 2). MK-571 (19μM) does not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2 alpha, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, MK-571 (19 μM) inhibits a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea[1]. In Vivo: MK-571 (L-660,711; i.v.) antagonizes bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but does not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal MK-571 antagonizes LTD4 (0.2-12.8 μg/kg)-induced bronchoconstriction in guinea pigs, and p.o. MK-571 blockes LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg)[1]. Hypoxia-exposed WT mice are treated with either saline or MK-571 (5 mg/kg/d or 25 mg/kg/d) for 2 more weeks while being maintain in hypoxic conditions. Saline-treated mice display all the hallmarks of PH (i.e., an increase in RVSP, Fulton index, and arterial wall thickness). However, following hypoxia, MK-571-treated mice display lower RVSP and Fulton index and a decrease in the medial thickening of small pulmonary arteries and arterioles[2].
