Hirasawa Y, Nishio M, Maeda K, Yoshida K, Kita Y
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Eur J Pharmacol. 1995 Jan 5;272(1):39-43. doi: 10.1016/0014-2999(94)0062s-5.
The anti-platelet effects of FK409 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide) , a new spontaneous nitric oxide releaser, and TRK-100 (sodium dl-4-[(1R,2R,3aS,8bS)-1,2,3a,8b-tetra-hydro-2-hydroxy-1-[(3S ,4RS)-3-hydroxy- 4-methyl-oct-6-yen-(E)-1-enyl]-5-cyclopenta[b]benzofuranyl]butyrate), a stable prostacyclin analogue, were studied both in vivo and in vitro. FK409 and TRK-100 inhibited ADP-induced platelet aggregation in rat platelet-rich plasma at 1.0 and 0.032 microM, respectively. In a rat extracorporeal shunt model, FK409 suppressed thrombus formation dose dependently and significantly at 1.0 mg/kg and showed the maximum inhibition (52% inhibition) at 10 mg/kg. TRK-100 showed 79% inhibition of thrombus formation at 1.0 mg/kg, but not at less than 1.0 mg/kg. At the doses required for antiplatelet effects, TRK-100 decreased mean blood pressure significantly but FK409 did not alter the blood pressure. These data suggest that FK409 shows more selective activities on platelets than TRK-100 in these experiments.
新型内源性一氧化氮释放剂FK409（(+/-)-(E)-乙基-2-[(E)-羟基亚氨基]-5-硝基-3-己烯酰胺）和稳定的前列环素类似物TRK-100（dl-4-[(1R,2R,3aS,8bS)-1,2,3a,8b-四氢-2-羟基-1-[(3S,4RS)-3-羟基-4-甲基-辛-6-烯-(E)-1-烯基]-5-环戊并[b]苯并呋喃基]丁酸酯钠）的抗血小板作用在体内和体外均进行了研究。FK409和TRK-100分别在1.0和0.032微摩尔浓度下抑制大鼠富含血小板血浆中ADP诱导的血小板聚集。在大鼠体外分流模型中，FK409在1.0毫克/千克时剂量依赖性且显著地抑制血栓形成，在10毫克/千克时显示出最大抑制作用（52%抑制）。TRK-100在1.0毫克/千克时显示出79%的血栓形成抑制率，但在低于1.0毫克/千克时则无此效果。在产生抗血小板作用所需的剂量下，TRK-100显著降低平均血压，但FK409不改变血压。这些数据表明，在这些实验中，FK409对血小板的选择性活性比TRK-100更高。
