Manent Jean-Bernard, Jorquera Isabel, Franco Valentina, Ben-Ari Yehezkel, Perucca Emilio, Represa Alfonso
INSERM U29, INMED, Marseille F-13009, France.
Epilepsy Res. 2008 Feb;78(2-3):131-9. doi: 10.1016/j.eplepsyres.2007.10.014. Epub 2007 Dec 31.
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/kg day) i.p.), a drug also endowed with GABAergic effects, and the new generation AEDs lamotrigine (LTG, 5-20mg/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 abnormalities 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.
孕期服用抗癫痫药物（AEDs）会引发严重且细微的胎儿畸形并伴有有害后遗症，这反映出有必要对这些药物的相对致畸潜力进行实验研究。我们最近报道，孕期接触两种通过GABA能机制起作用的AEDs——氨己烯酸和丙戊酸盐，会在啮齿动物中诱发海马体和皮质发育异常。我们现在研究了苯巴比妥（PB，腹腔注射30毫克/千克/天）、同样具有GABA能作用的药物以及新一代AEDs拉莫三嗪（LTG，腹腔注射5 - 20毫克/千克/天）、托吡酯（TPM，腹腔注射10毫克/千克/天）和左乙拉西坦（LEV，腹腔注射50毫克/千克/天）对大脑发育的影响。孕期接触LTG会以剂量依赖的方式诱发海马体和皮质畸形，母体血浆浓度处于临床常见范围内。接触PB、TP和LEV后未观察到这些异常。这些观察结果引发了对潜在临床相关性的担忧，并呼吁对孕期使用AEDs的后果进行详细的比较研究。
