Collins M D, Fradkin R, Scott W J
Children's Hospital Research Foundation, Cincinnati, Ohio.
Teratology. 1990 Jan;41(1):61-70. doi: 10.1002/tera.1420410107.
Exposure of A/J mice on day 9.5 of gestation to the derivatives of three acidic anticonvulsant agents, namely dimethadione, sodium valproate, and sodium diphenylhydantoin, each induced postaxial forelimb ectrodactyly predominantly of the right side. This specific malformation has previously been associated with the administration of acetazolamide to rodents; however, several agents can induce this same defect including other carbonic anhydrase inhibitors, carbon dioxide, cadmium, ethanol, ammonium chloride, and 13-cis retinoic acid. The relative potency of the three agents indicates no direct relationship to the pKa of the acid. Other than ectrodactyly, each of the anticonvulsant agents induced a compound-specific spectrum of malformations despite the uniform administration time. This finding suggests that these agents are capable of acting via different mechanisms or by the differential spatial and temporal dynamics of a common mechanism.
在妊娠第9.5天给A/J小鼠注射三种酸性抗惊厥药的衍生物，即二甲双酮、丙戊酸钠和苯妥英钠，每种药物都主要诱导右侧轴后肢缺指畸形。这种特定的畸形以前与给啮齿动物施用乙酰唑胺有关；然而，几种药物都能诱发相同的缺陷，包括其他碳酸酐酶抑制剂、二氧化碳、镉、乙醇、氯化铵和13-顺式视黄酸。这三种药物的相对效力表明与酸的pKa没有直接关系。除了肢端缺指畸形外，尽管给药时间一致，但每种抗惊厥药都诱导出一种化合物特异性的畸形谱。这一发现表明，这些药物能够通过不同的机制起作用，或者通过一种共同机制的不同时空动态起作用。
