Genotoxic effects of antiepileptic drugs. Literature review

Abstract

Based on the selected criteria data from studies of the genotoxic activity of antiepileptic drugs in eukaryotic test systems in vitro and in vivo, performed by DNA comet assay, chromosomal aberrations and micronuclei assays, published in the period 1995–2022, were selected and summarized.

Among the 20 drugs reviewed, for one drug (N03AA05 Benzobarbital), there are no data on studies of genotoxic activity; for 7 drugs information is presented only as a summary on the FDA and EMA websites without primary data and information on experimental designs. Among the remaining 12 drugs, only three drugs (phenobarbital, valproic acid and levetiracetam) have information on in vivo studies, both by DNA damage assay and by cytogenetic methods. Based on known publications, it is impossible to draw reasonable conclusions about the genotoxic potential of individual drugs. The available data are fragmentary, incomplete and contradictory. It remains to state the facts of detection of genotoxic effects in individual drugs in separate studies. In general, there is no doubt about the potential genotoxic hazard of this group the drugs in.

Additional studies are needed to clarify the data on the genotoxicity of antiepileptic drugs including beyond the standard protocols. In the course of their implementation, one should take into account the possible tissue-specific manifestation of antiepileptics genotoxicity, as indicated by the facts of genotoxic effects detection in tissue cells that are not targets in classical genotoxic studies. The expediency of objectifying approaches when choosing a drug for safe therapy, taking into account information about its genotoxicity, is emphasized, and the prospects for possible studies on antigenotoxic prophylaxis in patients with epilepsy are pointed out.

Keywords

antiepileptic drugs / chromosomal aberrations / micronuclei / DNA damage / genotoxicity

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