Ceserani R, Grossoni M, Ukmar G, Colombo M, Mongelli N
Prostaglandins Leukot Med. 1986 Mar;21(3):231-45. doi: 10.1016/0262-1746(86)90045-4.
FCE 22509, 5-(Z,E)-13,14-didehydro-20-methyl-carboprostacyclin, a chemically stable prostacyclin (PGI2) derivative, was 3.5 times more potent than PGI2 in relaxing bovine coronary artery in vitro; unlike PGI2, it did not contract bovine coronary vein and it antagonized PGI2-induced contractions of the coronary vein. In vitro smooth muscle (guinea pig ileum and trachea and rat stomach strip) was contracted to a lesser extent than with PGI2. FCE 22509 was about five times less potent than PGI2 in deaggregating platelet clumps formed on rabbit Achilles tendon bathed with heparinized cat blood (ED50 = 7.6 and 1.6 mcg/kg i.v. respectively). In the conscious normotensive and spontaneously hypertensive rat FCE 22509 lowered mean systemic arterial pressure (MSAP) (ED25 = 11.5 and 4.8 mcg/kg i.v.) to a lesser extent than PGI2 (ED25 = 2.1 and 2.34 mcg/kg i.v.) and increased heart rate but not dose-dependently. Orally administered, FCE 22509 likewise reduced MSAP though at high dosages (ED30 = 1.33 and 1.02 mg/kg in normotensive and hypertensive rats). Heart rate (HR) was raised after i.v. and oral treatment but not dose-dependently. In the open-chest anaesthetized dog, FCE 22509, compared with PGI2 at the same three doses, 0.2, 0.4 and 0.8 mcg/kg i.v., lowered MSAP but its hypotensive effect was less pronounced than that of PGI2. Like PGI2, FCE 22509 did not modify HR (though PGI2 showed a tendency to a decrease and FCE 22509 seemed to increase this cardiovascular function) and mean pulmonary arterial pressure (MPAP) and likewise significantly reduced myocardial contractile force. After infusion of PGI2 and FCE 22509 0.2 mcg/kg i.v. for 15 min in the open chest anaesthetized cat, the ex-vivo ADP-induced inhibition of platelet aggregation was the same for both compounds. Unlike PGI2, which reduced MSAP and MPAP, FCE 22509 had no significant lowering effect on MSAP and MPAP.
FCE 22509，即5-(Z,E)-13,14-二脱氢-20-甲基-卡前列环素，一种化学性质稳定的前列环素（PGI2）衍生物，在体外舒张牛冠状动脉方面的效力比PGI2高3.5倍；与PGI2不同，它不会使牛冠状静脉收缩，并且能拮抗PGI2诱导的冠状静脉收缩。在体外平滑肌（豚鼠回肠、气管和大鼠胃条）上，其收缩程度比PGI2小。在使浸有肝素化猫血的兔跟腱上形成的血小板凝块解聚方面，FCE 22509的效力比PGI2低约五倍（静脉注射的ED50分别为7.6和1.6微克/千克）。在清醒的正常血压和自发性高血压大鼠中，FCE 22509降低平均体动脉压（MSAP）（静脉注射的ED25分别为11.5和4.8微克/千克）的程度比PGI2（静脉注射的ED25分别为2.1和2.34微克/千克）小，并且会增加心率，但不是剂量依赖性的。口服FCE 22509同样能降低MSAP，不过需要高剂量（正常血压和高血压大鼠的ED30分别为1.33和1.02毫克/千克）。静脉注射和口服治疗后心率（HR）都会升高，但不是剂量依赖性的。在开胸麻醉的狗中，与相同的三个剂量（静脉注射0.2、0.4和0.8微克/千克）的PGI2相比，FCE 22509能降低MSAP，但其降压作用不如PGI2明显。与PGI2一样，FCE 22509不会改变心率（尽管PGI2有降低趋势，而FCE 22509似乎会增加这种心血管功能）和平均肺动脉压（MPAP），并且同样能显著降低心肌收缩力。在开胸麻醉的猫中静脉注射PGI2和FCE 22509 0.2微克/千克15分钟后，两种化合物对离体ADP诱导的血小板聚集的抑制作用相同。与降低MSAP和MPAP的PGI2不同，FCE 22509对MSAP和MPAP没有显著的降低作用。
