Levetiracetam (LEV) is the most potent O6 methylguanine DNA methyltransferase (MGMT)inhibitor among several antiepileptic drugs (AEDs) with diverse MGMT regulatory actions. In vitro, when used at concentrations within the human therapeutic range for seizure prophylaxis, LEV decreases MGMT protein and mRNA expression levels. Chromatin immunoprecipitation analysis reveals that LEV enhances p53 binding on the MGMT promoter by recruiting the mSin3A/histone deacetylase 1 (HDAC1) corepressor complex. However, LEV does not exert any MGMT inhibitory activity when the expression of either p53, mSin3A, or HDAC1 is abrogated. LEV inhibits malignant glioma cell proliferation and increases glioma cell sensitivity to the monofunctional alkylating agent temozolomide. In 4 newly diagnosed patients who had 2 craniotomies 7-14 days apart, prior to the initiation of any tumor-specific treatment, samples obtained before and after LEV treatment showed the inhibition of MGMT expression. This results suggest that the choice of AED in patients with malignant gliomas may have an unrecognized impact in clinical practice and research trial design 1).
Levetiracetam LEV may provide a survival benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated 2)
Levetiracetam appears effective and safe for seizure prevention in patients undergoing brain tumor resection and who are at significantly higher risk of developing post-operative seizures. These findings warrant confirmation in a prospective randomized trial 3).