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普特南、梅里特与苯妥英钠的发现。

Putnam, Merritt, and the discovery of Dilantin.

作者信息

Friedlander W J

出版信息

Epilepsia. 1986;27 Suppl 3:S1-20. doi: 10.1111/j.1528-1157.1986.tb05743.x.

Abstract

In the first part of this essay, the "common wisdom" about Putnam and Merritt's contributions to the treatment of epilepsy was summarized (Rowland, 1982). Based on the history that has been presented here, how true are these "wisdoms"? Putnam and Merritt did devise "a simple and reliable method to test drugs of anticonvulsant effect" and they did show "that anticonvulsant effects in cats accurately predicted effects in humans," but others before them had done these same things. Dilantin, contrary to common wisdom, was not the first anticonvulsant drug to be tested in animals before it was given to human subjects; at least a year before, Cobb and his co-workers had done the same thing using vital dyes. However, Dilantin did represent the first time an anticonvulsant tested in animals was subsequently studied in a large series of patients. Nor were Putnam and Merritt the first to show that "anticonvulsant and sedative effects of drugs could be separated." Potassium borotartrate, ketogenic diet, ketone bodies, and vital dyes were anticonvulsive without necessarily being sedative. However, Putnam and Merritt were probably the first to make so explicit a statement to this effect. It may well have been this particular statement--and the fact that it was so well heard by other researchers--that represented their greatest achievement. In Kuhn's theory of scientific revolutions, the great step forward may not be so much the accumulation of evidence that the existing paradigm is not a feasible one, but rather the use of this evidence to form a new model or paradigm which is then accepted by normal science in such a fashion that the results prove to be productive. This, it would seem, is what Putnam and Merritt did. From it came their own major discovery, Dilantin, which, in Rowland's words, remains "a mainstay of treatment" for epilepsy up to the present time, and which "opened the way to the development of other anticonvulsant drugs."

摘要

在本文的第一部分,总结了关于普特南和梅里特对癫痫治疗贡献的“普遍看法”(罗兰,1982年)。基于此处呈现的历史,这些“看法”有多正确呢?普特南和梅里特确实设计出了“一种简单可靠的方法来测试抗惊厥药物的效果”,并且他们确实表明“猫身上的抗惊厥效果能准确预测对人类的效果”,但在他们之前就有人做过同样的事情。与普遍看法相反,苯妥英钠并非第一种在用于人体试验之前先在动物身上进行测试的抗惊厥药物;至少在一年前,科布和他的同事就使用活性染料做过同样的事情。然而,苯妥英钠确实代表了首次在动物身上测试的抗惊厥药物随后在大量患者中进行研究。普特南和梅里特也不是第一个表明“药物的抗惊厥和镇静作用可以分开”的人。酒石酸硼钾、生酮饮食、酮体和活性染料具有抗惊厥作用,但不一定有镇静作用。然而,普特南和梅里特可能是第一个如此明确地表述这一观点的人。很可能正是这一特定表述——以及它被其他研究人员广泛接受这一事实——代表了他们最大的成就。在库恩的科学革命理论中,向前迈出的一大步可能不在于积累现有范式不可行的证据,而在于利用这些证据形成一个新的模型或范式,然后被常规科学所接受,其结果被证明是富有成效的。看起来,这就是普特南和梅里特所做的。由此产生了他们自己的重大发现——苯妥英钠,用罗兰的话说,直到现在它仍然是癫痫治疗的“中流砥柱”,并且“为其他抗惊厥药物的开发开辟了道路”。

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