Antiepileptic drugs and brain maturation: Fetal exposure to lamotrigine generates cortical malformations in rats

Jean Bernard Manent, Isabel Jorquera, Valentina Franco, Yehezkel Ben-Ari, Emilio Perucca, Alfonso Represa

Research output: Contribution to journalArticle

Abstract

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, 5-20 mg/kg/day i.p.), topiramate (TPM, 10 mg/kg/day i.p.), and levetiracetam (LEV, 50 mg/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.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalEpilepsy Research
Volume78
Issue number2-3
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Antiepileptic drugs
  • Cortical malformations
  • Fetal development
  • Lamotrigine
  • Rats

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Neurology

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