Birch J, Brown E, Calnan C, Jessup C L, Jessup R, Wayne M
ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
J Pharm Pharmacol. 1988 Oct;40(10):706-10. doi: 10.1111/j.2042-7158.1988.tb06999.x.
The effects of ICI 185,282 (5(Z)-7-([ 2,4,5-cis]-4-O-hydroxyphenyl-2-trifluoromethyl-1, 3-dioxan-5-yl)heptenoic acid) have been studied on guinea-pig platelets and pulmonary smooth muscle in-vitro and in-vivo. When tested on guinea-pig lung parenchyma in-vitro. ICI 185,282 (1 x 10(-7) M) produced a significant shift in U-46619 response curves (concentration ratio of 13:3); the antagonist (1 x 10(-5) M) did not modify histamine responses. When tested on guinea-pig trachea in-vitro ICI 185,282 (1 x 10(-7) M) caused significant inhibition of U-46619 and PGD2 responses (concentration ratios of 8.3 and 14.1, respectively); the antagonist (1 x 10(-5) M proved less effective against contractions of PGF2 alpha, LTD4 and histamine (concentration ratios of 7.0, 1.5 and 1.6). When added to guinea-pig platelet rich plasma in-vitro, ICI 185,282 (x 10(-6), 1 x 10(-5) M) caused concentration-dependent parallel shifts to the right of U-46619 aggregation curves, yielding concentration ratios of 13.6 and 141.9, respectively. In-vitro, addition of ICI 185,282 (x 10(-5) M) to indomethacin-treated pulmonary smooth muscle did not modify resting tone, neither did it induce aggregation or swelling in platelet-rich plasma preparations. When administered orally to guinea-pigs ICI 185,282 (0.1, 0.5 mg kg-1) caused a significant inhibition of U-46619-induced platelet aggregation ex-vivo which persisted greater than or equal to 8 h. In-vivo, a single oral dose of ICI 185,282 (1 mg kg-1) inhibited bronchospasm induced by U-46619, PGD2, PGF2 alpha, arachidonic acid, LTD4 and PAF; responses to histamine were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
已在体外和体内研究了ICI 185,282（5(Z)-7-([2,4,5-顺式]-4-O-羟基苯基-2-三氟甲基-1,3-二氧杂环己烷-5-基)庚烯酸）对豚鼠血小板和肺平滑肌的作用。在体外对豚鼠肺实质进行测试时，ICI 185,282（1×10⁻⁷ M）使U-46619反应曲线发生显著右移（浓度比为13:3）；拮抗剂（1×10⁻⁵ M）未改变组胺反应。在体外对豚鼠气管进行测试时，ICI 185,282（1×10⁻⁷ M）显著抑制U-46619和PGD₂反应（浓度比分别为8.3和14.1）；拮抗剂（1×10⁻⁵ M）对PGF₂α、LTD₄和组胺收缩的抑制效果较差（浓度比分别为7.0、1.5和1.6）。当体外添加到豚鼠富含血小板的血浆中时，ICI 185,282（1×10⁻⁶、1×10⁻⁵ M）使U-46619聚集曲线浓度依赖性地平行右移，浓度比分别为13.6和141.9。体外，向吲哚美辛处理的肺平滑肌中添加ICI 185,282（1×10⁻⁵ M）未改变静息张力，在富含血小板的血浆制剂中也未诱导聚集或肿胀。口服给予豚鼠ICI 185,282（0.1、0.5 mg·kg⁻¹）可显著抑制体外U-46619诱导的血小板聚集，这种抑制持续≥8小时。在体内，单次口服剂量的ICI 185,282（1 mg·kg⁻¹）可抑制U-46619、PGD₂、PGF₂α、花生四烯酸、LTD₄和PAF诱导的支气管痉挛；对组胺的反应未受影响。（摘要截断于250字）
