TY - JOUR
T1 - Antiepileptic drugs and brain maturation
T2 - Fetal exposure to lamotrigine generates cortical malformations in rats
AU - Manent, Jean Bernard
AU - Jorquera, Isabel
AU - Franco, Valentina
AU - Ben-Ari, Yehezkel
AU - Perucca, Emilio
AU - Represa, Alfonso
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - Antiepileptic drugs
KW - Cortical malformations
KW - Fetal development
KW - Lamotrigine
KW - Rats
UR - http://www.scopus.com/inward/record.url?scp=38549100026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38549100026&partnerID=8YFLogxK
U2 - 10.1016/j.eplepsyres.2007.10.014
DO - 10.1016/j.eplepsyres.2007.10.014
M3 - Article
C2 - 18166379
AN - SCOPUS:38549100026
VL - 78
SP - 131
EP - 139
JO - Epilepsy Research
JF - Epilepsy Research
SN - 0920-1211
IS - 2-3
ER -