levetiracetam + temozolomide

Levetiracetam + temozolomide is a combination of two small molecule drugs used primarily in the management of glioblastoma and other malignant gliomas. Levetiracetam is an antiepileptic drug that binds to synaptic vesicle protein SV2A, modulating neurotransmitter release and inhibiting calcium channels, thereby controlling seizures in brain tumor patients. Temozolomide is an oral alkylating agent that induces DNA damage by methylating guanine residues, leading to tumor cell death. Recent research indicates that levetiracetam can enhance the efficacy of temozolomide by epigenetically silencing O6-methylguanine-DNA methyltransferase (MGMT) through increased histone deacetylase activity (notably HDAC1/HDAC4), which reduces MGMT-mediated DNA repair and increases tumor sensitivity to temozolomide-induced cytotoxicity. This combination has shown promise in overcoming resistance to temozolomide, particularly in MGMT-positive glioma cells, potentially improving survival outcomes for patients with glioblastoma[1][2][3][5][6][7].