Valproate-induced developmental modifications maybe partially prevented by coadministration of folinic acid and S-adenosylmethionine.

Neural Tube Defects (NTD) are congenital anomalies caused by a wide range of different factors, including both genetic and environmental effects, which include severe lesions such as anencephaly and microcephaly and anomalies commonly known as spines bifidas. Folic acid seems to be involved in the prevention of this type of defects. The most conclusive studies showed that periconceptional administration of multivitamins, specially folate, reduces the recurrence risk of NTD in a 50 to 66% of the cases (MRC Vitamin Study Research Group, 1991), Antiepileptic agents such as Valproic acid (VPA) are known teratogenic agents highly specific for the induction of NTD. Furthermore, it also induce a wide range of skull malformations and tissues alterations. This agent are also recognized as interferer of folate metabolism. Folate concentrations decrease during normal pregnancy and treatment with antiepileptic drugs, including VPA. intensities this effect. Futhermore, several reports suggest that epileptic patiens with malformed infants had particularly low levels of folate in their plasma (Ogawa el ar., 1991), The molecular mechanism of the teratogenicity of VPA is not well known, bul one of the h othesis ro osed is that VPA interacts with emb 0 folate metabolism Nau, 1994).