A SHORT HISTORY OF THALIDOMIDE EMBRYOPATHY
A SHORT HISTORY OF THALIDOMIDE EMBRYOPATHY
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DOI：
10.1002/tera.1420380303
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发表时间：
1988-09-01
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影响因子：
--
通讯作者：
LENZ, W
中科院分区：
文献类型：
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作者：
LENZ, W
在沙利度胺的首次合成和专利申请之后，沙利度胺的临床试验于1954年4月开始。对该物质进行了痉挛、局部麻醉和抗惊厥作用试验。它被认为具有抗组胺和抗麦角活性，正如其德语名称Contergan所示。当三名患有痉挛性便秘的女性尝试使用沙利度胺时，意外地发现它可以诱导睡眠。临床试验包括植物性肌张力障碍、肺结核、流感、百日咳、高血压、动脉粥样硬化、甲状腺功能亢进、神经源性胃病和肝病患者。1956年11月，沙利度胺以Grippex的名称上市，表明它应该有助于对抗“Grippe”，即流感。1956年8月，印刷了一份传单，列举了以下适应症：易怒、注意力不集中、怯场、早泄、月经紧张、绝经后症状、害怕检查、胃和胆囊功能障碍、发热性传染病、轻度抑郁、焦虑、甲状腺功能亢进和结核病。这种多效药物几乎没有副作用的说法被提出并坚持了好几年。1957年11月，康特根在有效的宣传活动的支持下投放市场。当时，众所周知，许多化学物质，包括一些对成人急性毒性低的化学物质，可能会损害胎儿。到1950年，安塞尔在他的专著《La Chimioteratogkn&se，Realisation des Monstruosites par des Substances Chimiques chez les Vertebres》中分析了490篇已发表论文中报道的实验结果。1958年，威利斯在他的书《胚胎学和病理学的边界》中指出：“值得注意的是，只有少数化学制剂在哺乳动物中进行了致畸作用的测试，这些药物不包括任何常用的生物碱。
Immediately following the first synthesis of thalidomide, and patent application, clinical trials with thalidomide were started in April 1954. The substance was tested for spasmolytic, local anesthetic and anticonvulsive effects. It was supposed to have antihistamine and antiergotropic activity as indicated by its German name Contergan. When thalidomide was tried in three women with spastic constipation, it was unexpectedly found to induce sleep. Clinical trials included patients with vegetative dystonia, tuberculosis, influenza, pertussis, hypertension, atherosclerosis, hyperthyroidism, gastric complaints of nervous origin, and liver disease. In November 1956, thalidomide was marketed under the name of Grippex, indicating that it was supposed to be helpful against “Grippe”, ie, influenza. In August 1956, a leaflet was printed enumerating the following indications: irritability, weak concentration, stage fright, ejaculatio praecox, menstrual tension, postmenopausal symptoms, fear of examination, functional disorders of the stomach and gallbladder, febrile infectious diseases, mild depression, anxiety, hyperthyroidism, and tuberculosis. The claim was raised and maintained for several years that such a multipotent drug was virtually free from side effects.In November 1957, Contergan was launched on the market, supported by an effective propaganda campaign. At that time it was well known that many chemical substances, including some with low acute toxicity in adults, might damage the fetus. By 1950, Ancel, in his monograph “La Chimioteratogkn&se, Realisation des Monstruosites par des Substances Chimiques chez les Vertebres,” had analyzed the results of experiments reported in 490 published papers. In 1958, Willis, in his book “The Borderline of Embryology and Pathology,” stated:“It will be noted that only a few chemical agents have yet been tested for teratogenic effects in mammals, and that these do not include any of the commonly used alkaloids,