Teratogenic action of acetazolamide in golden hamsters.
Teratogenic action of acetazolamide in golden hamsters.
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乙酰唑胺对金黄仓鼠的致畸作用。
DOI：
10.1002/tera.1420040113
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发表时间：
1971
期刊：
影响因子：
--
通讯作者：
W. M. Layton
中科院分区：
文献类型：
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作者：
W. M. Layton
碳酸酐酶抑制剂乙酰唑胺在妊娠第9天以300-1200 mg/kg的剂量单次腹腔给药时对金黄地鼠有致畸作用。大多数畸形是前肢的轴后部分。ED 50为695 mg/kg，存在明确的剂量-反应关系。交配后192-210 h为敏感期，204 h为高峰。这种畸形的产生与显著的胚胎死亡率无关。乙酰唑胺是非常具体的，除了手畸形，只有少数足部畸形和罕见的露脑畸形的情况下产生。与大鼠相反，乙酰唑胺诱导的畸形几乎完全是右前肢的轴后部分，仓鼠的畸形发生在任何前肢，虽然当一个单一的后足畸形，它总是左。所证明的敏感期是在肢芽形成期间，并且在给药后24小时观察到畸形的第一外部体征为肢芽的轴后边缘变平。乙酰唑胺的作用机制尚不清楚，因为致畸剂量可能超过完全抑制碳酸酐酶活性所需的量。所需的剂量也比用于人类治疗的剂量大得多，因此这种药物似乎对人类没有致畸性危害。
The carbonic-anhydrase inhibitor acetazolamide was teratogenic for golden hamsters when given in single intraperitoneal doses of from 300-1200 mg/kg on the 9th day of pregnancy. Most deformities were of the postaxial part of the forelimb. There was a well-defined dose-response relation with an ED50 of 695 mg/kg. A sensitive period was demonstrated from 192–210 hours after mating with a peak at 204 hours. The production of this deformity was not associated with a significant embryonic mortality. Acetazolamide is quite specific in that in addition to hand deformities only a few foot deformities and rare cases of exencephaly were produced. In contrast to rats, where acetazolamide-induced deformities are almost exclusively of the postaxial portion of the right forelimb, the deformity in hamsters occurred in either forelimb, although when a single hindfoot was malformed it was always the left one. The demonstrated sensitive period is during the time of limbbud formation, and the first external signs of deformity were seen as a flattening of the postaxial margins of the limb bud 24 hours after drug administration. The mechanism of action of acetazolamide is not clear since the teratogenic dose probably exceeds the amount needed for complete inhibition of carbonic-anhydrase activity. The dose needed is also much greater than that used for human therapy, so it does not appear that this drug is a teratogenic hazard for human beings.