P17.73 * IN VITRO ANALYSIS OF CYTOTOXIC EFFECTS OF BRIVARACETAM AND LACOSAMIDE ON HUMAN GLIOBLASTOMA CELLS

Abstract

RATIONAL AND AIMS: Epilepsy is a frequent side effect in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patient are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of drug-resistant epilepsy affected patients suggesting their involvement in the clearance of antiepileptic medications. In addition to the action anticonvulsant drugs has been documented for some a possible cytotoxic effect. METHODS: The in vitro effects of two new generation antiepileptic drugs, Brivaracetam and Lacosamide, were evaluated on two lines of human glioblastoma (A172 and U87). RESULTS: The results show a cytotoxic effect of Brivaracetam and Lacosamide on the cell line U87. However, the cytotoxic mechanism does not appear to be related to apoptosis, evaluated by annexin V binding. Moreover, by flow cytometric analysis, we observed that exposure of the two cell lines to Brivaracetam or Lacosamide at their IC30 does not contribute to the modulation of the chemoresistance molecules MRP1, MRP3, MRP5, GSTπ and P-Gp. Similar results were obtained by evaluating the modulation of the same molecules on human umbilical vein endothelial cells (HUVEC) after exposure to the two drugs. CONCLUSIONS: The data obtained suggest that Brivaracetam and Lacosamide in vitro play a cytotoxic effect on human glioma cells.