Willis A L, Smith D L, Vigo C, Kluge A, O'Yang C, Kertesz D, Wu H
Institute of Experimental Pharmacology, Syntex Research, Palo Alto, California 94304.
Adv Prostaglandin Thromboxane Leukot Res. 1987;17A:254-65.
RS-93427 is a potent, orally active prostacyclin-mimetic that is very rapidly absorbed but with generally long-lived actions in most species. It has antithrombotic, thrombolytic, and antivasospastic potential. Alone among several tested PGI-mimetics, it inhibits release of platelet mitogens more potently than its ability to inhibit aggregation. It also inhibits mitogen release from macrophages and vascular endothelial cells. RS-93427 is also potent at inhibiting macrophage accumulation of cholesteryl esters. These data suggest a broad spectrum of potential therapeutic utility for RS-93427 via the oral route. It might be useful both in acute manifestations of vascular occlusive disease involving thrombosis and vasospasm, in addition to the more chronic conditions involving intimal hyperplasia (as in arteriovenous grafts) and possibly frank atherosclerosis. Much work remains to be done, including examination of RS-93427 in chronic studies with various dosage forms, particularly in the study of atherosclerosis.
RS - 93427是一种强效的、口服活性的前列环素模拟物，吸收非常迅速，但在大多数物种中作用通常持久。它具有抗血栓形成、溶栓和抗血管痉挛的潜力。在几种经过测试的前列环素模拟物中，它单独抑制血小板有丝分裂原释放的能力比抑制聚集的能力更强。它还抑制巨噬细胞和血管内皮细胞释放有丝分裂原。RS - 93427在抑制巨噬细胞胆固醇酯积累方面也很有效。这些数据表明，RS - 93427通过口服途径具有广泛的潜在治疗用途。它可能对涉及血栓形成和血管痉挛的血管闭塞性疾病的急性表现有用，此外对涉及内膜增生（如动静脉移植物）以及可能的明显动脉粥样硬化的更慢性疾病也有用。仍有许多工作要做，包括用各种剂型对RS - 93427进行慢性研究，特别是在动脉粥样硬化研究中。
