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拉莫三嗪对大鼠胎儿脑的致畸作用:一项形态计量学研究。

Teratogenic effects of lamotrigine on rat fetal brain: a morphometric study.

作者信息

Marchi N S, Azoubel R, Tognola W A

机构信息

Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil.

出版信息

Arq Neuropsiquiatr. 2001 Jun;59(2-B):362-4. doi: 10.1590/s0004-282x2001000300010.

DOI:10.1590/s0004-282x2001000300010
PMID:11460180
Abstract

A study of the teratogenic activity of an antiepileptic drug - lamotrigine - was carried out in the brain of fetuses of rats who had received the drug. The dosage levels studied corresponded to four times the median effective dose (ED50) in rats. The drug was administered during the organogenesis period. Rats were sacrificed one day prior to term and fetuses were macroscopically examined, weighted and cephalic segments sectioned (Wilson technique), for histological study by stereological analysis, using Merz's grid for drawing and point counts. Cortex, subcortex, ependyma and lateral ventricles were analyzed. The same methodology was applied to the control group; data were compared with by the non-parametric Mann-Whitney statistical analysis test. Results showed that fetuses of the experimental group had reduced body weight at birth, increased volume and diameter of the cerebral structure, increased density of the subcortical layer, and ventricle dilatation. Possible mechanisms of this teratogenicity were discussed.

摘要

对一种抗癫痫药物——拉莫三嗪——的致畸活性进行了研究,研究对象为服用该药物的大鼠胎儿的大脑。所研究的剂量水平相当于大鼠半数有效剂量(ED50)的四倍。该药物在器官形成期给药。在足月前一天处死大鼠,对胎儿进行大体检查、称重,并将头部切片(威尔逊技术),通过体视学分析进行组织学研究,使用默茨网格进行绘图和点计数。对皮质、皮质下、室管膜和侧脑室进行了分析。对对照组采用相同的方法;通过非参数曼-惠特尼统计分析检验对数据进行比较。结果显示,实验组胎儿出生时体重减轻,脑结构体积和直径增加,皮质下层密度增加,脑室扩张。讨论了这种致畸性的可能机制。

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Ameliorative effects of supplemental folinic acid on Lamotrigine-induced fetal malformations in the mouse.补充叶酸对拉莫三嗪致小鼠胎儿畸形的改善作用。
Mol Cell Biochem. 2018 Sep;446(1-2):185-197. doi: 10.1007/s11010-018-3285-0. Epub 2018 Jan 23.
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Teratogenicity of antiepileptic medications.抗癫痫药物的致畸性。
Semin Neurol. 2008 Jul;28(3):328-35. doi: 10.1055/s-2008-1079337. Epub 2008 Jul 24.
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Antiepileptic drugs and neurodevelopment.抗癫痫药物与神经发育
Curr Neurol Neurosci Rep. 2006 Jul;6(4):341-6. doi: 10.1007/s11910-006-0028-5.
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Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo.拉莫三嗪在体外人胎盘灌注系统以及体内母体和脐带血中的经胎盘转运。
Eur J Clin Pharmacol. 2003 Feb;58(10):677-82. doi: 10.1007/s00228-002-0544-4. Epub 2003 Jan 30.