Nishio S, Kurumatani H
Pharmaceutical Research Laboratories, Toray Industries Inc., 1111 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Shintaro
Nihon Yakurigaku Zasshi. 2001 Feb;117(2):123-30. doi: 10.1254/fpj.117.123.
Prostacyclin is an endogeneous eicosanoid synthesized by vascular endothelial cells, and has potent inhibitory effects on platelet adhesion/aggregation and vasoconstriction. However, its therapeutic use is restricted by its extremely short half-life. Beraprost sodium (beraprost) is the first orally active prostacyclin analogue developed by TORAY Industries, Inc. Beraprost possesses a phenol moiety instead of the exo-enol ether moiety, which is the cause of the instability of prostacyclin, and has a modified omega-side chain that contributes to dissociating antiplatelet action from adverse reactions. In 1992, beraprost was approved as a drug for chronic arterial occlusion. Beraprost is now widely used clinically as "Dorner" or "Procylin". The indication for "primary pulmonary hypertension" was also approved in 1999. Recently in Europe, a placebo controlled trial named "Beraprost et Claudication Intermittent-2 (BERCI-2)" was performed, and it was reported that beraprost improved the walking distances of the patients. Beraprost has a variety of biological activities such as antiplatelet effects, vasodilation effects, antiproliferative effects on vascular smooth muscle cells, cytoprotective effects on endothelial cells and inhibitory effects on the production of inflammatory cytokines. On the basis of basic and clinical research, it has been suggested that beraprost is also effective for many intractable diseases. We expect that the relationship between reduced prostacyclin level and these diseases would be clarified and the beneficial effects of beraprost would be demonstrated by controlled clinical trials in the future.
前列环素是一种由血管内皮细胞合成的内源性类花生酸，对血小板黏附/聚集和血管收缩具有强大的抑制作用。然而，其治疗用途因其极短的半衰期而受到限制。贝前列素钠（贝拉普司特）是东丽工业株式会社研发的首个口服活性前列环素类似物。贝拉普司特具有一个酚基团而非前列环素不稳定的原因——外烯醇醚基团，并且具有一个经过修饰的ω侧链，这有助于将抗血小板作用与不良反应分离。1992年，贝拉普司特被批准作为治疗慢性动脉闭塞的药物。贝拉普司特现在临床上广泛以“Dorner”或“Procylin”的名称使用。1999年，其“原发性肺动脉高压”的适应证也获得批准。最近在欧洲，进行了一项名为“贝前列素与间歇性跛行-2（BERCI-2）”的安慰剂对照试验，据报道贝拉普司特改善了患者的步行距离。贝拉普司特具有多种生物学活性，如抗血小板作用、血管舒张作用、对血管平滑肌细胞的抗增殖作用、对内皮细胞的细胞保护作用以及对炎性细胞因子产生的抑制作用。基于基础和临床研究，有人提出贝拉普司特对许多难治性疾病也有效。我们期望未来通过对照临床试验能够阐明前列环素水平降低与这些疾病之间的关系，并证明贝拉普司特的有益作用。
