Antiepileptic drugs and brain maturation: Fetal exposure to lamotrigine generates cortical malformations in rats
Antiepileptic drugs and brain maturation: Fetal exposure to lamotrigine generates cortical malformations in rats
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DOI：
10.1016/j.eplepsyres.2007.10.014
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发表时间：
2008-02-01
影响因子：
2.2
通讯作者：
Represa, Alfonso
中科院分区：
文献类型：
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作者：
Manent, Jean-Bernard;Jorquera, Isabel;Represa, Alfonso
妊娠期间摄入抗癫痫药物（AEDs）可引起严重和微妙的胎儿畸形与有害的后遗症，反映了这些药物的比较致畸潜力的实验研究的必要性。我们最近报道，产前暴露于氨己烯酸和丙戊酸盐，两种通过GABA能机制发挥作用的AED，诱导啮齿动物海马和皮质发育不良。我们现在已经研究了苯巴比妥（PB，30 mg/kg/天）i. p.），也具有GABA能作用的药物，以及新一代AEDs拉莫三嗪（LTG，5-20 mg/kg/天i. p.），托吡酯（TPM，10 mg/kg/天，i. p.），和左乙拉西坦（LEV，50 mg/kg/天i. p.）对大脑发育的影响产前暴露于LTG诱导海马和皮质畸形的剂量依赖性的方式，在母体血浆浓度在临床发生的范围内。经PB、TP和LEV暴露后，未观察到这些异常。这些观察结果引起了对潜在临床相关性的关注，并呼吁对妊娠期间使用AED的后果进行详细的比较研究。(C)2007 Elsevier B. V.保留所有权利。
Intake of antiepileptic drugs (AEDs) during pregnancy can provoke severe and subtle fetal malformations associated with deleterious sequelae, reflecting the need for experimental investigations on the comparative teratogenic potential of these agents. We recently reported that prenatal exposure to vigabatrin and valproate, two AEDs which act through GABAergic mechanisms, induces hippocampal and cortical dysplasias in rodents. We have now investigated the effects of phenobarbital (PB, 30 mg/kgday) i.p.), a drug also endowed with GABAergic effects, and the newgeneration AEDs lamotrigine (LTG, 5-20 mg/kg/day i.p.), topiramate (TPM, 10mg/kg/day i.p.), and levetiracetam (LEV, 50mg/kg/day i.p.) on brain development. Prenatal exposure to LTG induced hippocampal and cortical malformations in a dose-dependent manner, at maternal plasma concentrations within the clinically occurring range. These abnormatities were not observed after exposure to PB, TP and LEV. These observations raise concerns about potential clinical correlates and call for detailed comparative investigations on the consequences of AED use during pregnancy. (C) 2007 Elsevier B.V. All rights reserved.