Sim A K, McCraw A P, Cleland M E, Nishio S, Umetsu T
Arzneimittelforschung. 1985;35(12):1816-8.
Sodium dl-4-[1R,2R,3aS,8bS)-1,2,3a,8b-tetrahydro- 2-hydroxy-1-[(3S,4RS)-3-hydroxy-4-methyl-oct-6- yne-(E)-1-enyl]-5-cyclopenta[b]benzofuranyl]butyrate (TRK-100) is a stable analogue of prostacyclin (epoprostenol, PGI2). The drug was shown to be a potent inhibitor of platelet aggregation in vitro, induced by adenosine diphosphate (ADP), using platelet-rich plasma (PRP) from human and several animal species. The inhibitory activity of TRK-100 using human platelets was half that of PGI2 and eight times that of PGE1. There was a marked tendency for platelet clumps to disaggregate following secondary aggregation in the presence of TRK-100 at final concentrations higher than 1 ng/ml. This activity was similar to PGI2 and more than 30 times that of PGE1. TRK-100 was shown to induce the disaggregation of a pre-existing thrombus in the microcirculation of the hamster cheek pouch. A dose-dependent response was obtained following oral administration of the drug at levels of 50-200 micrograms/kg. Optimal activity was observed 30-60 min after dosing and activity was sustained throughout the experimental period. TRK-100 was more active than PGE1 in the test system and appeared to be of a similar potency to PGI2. Since this drug is stable, orally active and without the hypotensive activity of PGI2, it is considered to be a potentially useful agent for antithrombotic therapy.
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-炔-(E)-1-烯基]-5-环戊二烯并[b]苯并呋喃基]丁酸钠（TRK-100）是前列环素（依前列醇，PGI2）的稳定类似物。使用来自人和几种动物物种的富血小板血浆（PRP），该药物在体外被证明是由二磷酸腺苷（ADP）诱导的血小板聚集的有效抑制剂。使用人血小板时，TRK-100的抑制活性是PGI2的一半，是PGE1的八倍。在最终浓度高于1 ng/ml的TRK-100存在下，二次聚集后血小板团块有明显的解聚趋势。这种活性与PGI2相似，是PGE1的30倍以上。TRK-100被证明可诱导仓鼠颊囊微循环中预先形成的血栓解聚。口服该药物剂量为50-200微克/千克时获得了剂量依赖性反应。给药后30-60分钟观察到最佳活性，并且在整个实验期间活性持续存在。在测试系统中，TRK-100比PGE1更具活性，并且似乎与PGI2具有相似的效力。由于该药物稳定、口服活性且没有PGI2的降压活性，因此被认为是抗血栓治疗的潜在有用药物。
