Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease
Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease
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DOI：
10.1093/toxsci/kfr088
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发表时间：
2011-07-01
影响因子：
3.8
通讯作者：
Scialli, Anthony R.
中科院分区：
文献类型：
--
作者：
Kim, James H.;Scialli, Anthony R.
沙利度胺是20世纪50年代末和60年代初广泛使用的药物，用于治疗孕妇恶心。在20世纪60年代，沙利度胺治疗导致数千名儿童出现严重的出生缺陷。虽然当时大多数国家禁止使用沙利度胺，但沙利度胺被证明是麻风病和后来的多发性骨髓瘤的有效治疗方法。在世界上缺乏广泛医疗监测举措的农村地区，沙利度胺治疗麻风病孕妇继续导致畸形。对沙利度胺作用机制的研究有助于更好地了解分子靶点。随着对这些分子靶点的进一步了解，可以设计出更安全的药物。沙利度胺悲剧标志着毒性测试的一个转折点，因为它促使美国和国际监管机构制定系统的毒性测试协议;沙利度胺作为发育生物学工具的使用导致了肢体发育生化途径的重要发现。在庆祝毒理学学会成立50周年之际，恰逢沙利度胺退出市场50周年，重温20世纪60年代沙利度胺悲剧的教训是合适的。
Thalidomide was a widely used drug in the late 1950s and early 1960s for the treatment of nausea in pregnant women. It became apparent in the 1960s that thalidomide treatment resulted in severe birth defects in thousands of children. Though the use of thalidomide was banned in most countries at that time, thalidomide proved to be a useful treatment for leprosy and later, multiple myeloma. In rural areas of the world that lack extensive medical surveillance initiatives, thalidomide treatment of pregnant women with leprosy has continued to cause malformations. Research on thalidomide mechanisms of action is leading to a better understanding of molecular targets. With an improved understanding of these molecular targets, safer drugs may be designed. The thalidomide tragedy marked a turning point in toxicity testing, as it prompted United States and international regulatory agencies to develop systematic toxicity testing protocols; the use of thalidomide as a tool in developmental biology led to important discoveries in the biochemical pathways of limb development. In celebration of the Society of Toxicology's 50th Anniversary, which coincides with the 50th anniversary of the withdrawal of thalidomide from the market, it is appropriate to revisit the lessons learned from the thalidomide tragedy of the 1960s.