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Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics
Author(s) -
GefrohGrimes H. A.,
Gidal B. E.
Publication year - 2016
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.12437
Subject(s) - levetiracetam , valproic acid , carbamazepine , epigenetics , medicine , pharmacokinetics , histone deacetylase , pharmacology , epilepsy , lacosamide , methyltransferase , drug , dna methylation , histone , methylation , biology , genetics , gene , psychiatry , gene expression
In neurological malignancies, antiepileptic drugs ( AED s) are frequently used to control the seizure activity that accompanies the disorder. There is a growing body of evidence on the importance of AED selection for reasons other than pharmacokinetics ( PK ) properties. Epigenetic modifications may occur in glioblastomas, such as changes in gene methylation and histone acetylation states. Secondary mechanisms of AED drug action which impact these epigenetic modifications could play a significant role in patient survival outcomes. Both valproic acid ( VPA ) and carbamazepine have histone deacetylase ( HDAC ) inhibitory activities, and levetiracetam and VPA reduce the activity of O6‐methylguanine‐ DNA methyltransferase ( MGMT ), a DNA ‐repair molecule implicated in resistance to alkylating agents used for chemotherapy. The use of AED s for purposes other than seizure prophylaxis and their selection based on non‐ PK properties present a potential paradigm shift in the field of neuro‐oncology.