MK-571 SODIUM HYDRATE性质、用途与生产工艺
MK-571 sodium salt是一种选择性，口服活性的白三烯D4受体拮抗剂，在豚鼠和人肺膜的Ki分别为0.22 和 2.1 nM。
|
LTD
4
0.22 nM (Ki, In guinea pig lung)
|
LTD
4
2.1 nM (Ki, In human lung)
|
MK-571 (L660,711) is a potent and selective competitive inhibitor of [
3
H]leukotriene D4 binding in guinea pig (K
i
value, 0.22 nM) and human (K
i
value, 2.1 nM) lung membranes. MK-571 is essentially inactive versus [
3
H]LTC4 binding with IC
50
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) D
4
(respective pA
2
values, 9.4 and 10.5) and LTE4 (respective pA
2
values, 9.1 and 10.4) and contractions of human trachea induced by LTD
4
(pA
2
value, 8.5). MK-571 (58 nM) antagonizes contractions of guinea pig trachea induced by LTC
4
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, PGF
2
alpha, U-44069, or PGD
2
. 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.
MK-571 (L-660,711; i.v.) antagonizes bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC
4
, LTD
4
, and LTE
4
but does not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal MK-571 antagonizes LTD
4
(0.2-12.8 μg/kg)-induced bronchoconstriction in guinea pigs, and p.o. MK-571 blockes LTD
4
- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg). 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.
MK-571 SODIUM HYDRATE
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