Effects of antiepileptic drugs on mitochondrial functions, morphology, kinetics, biogenesis, and survival

Date
2017Author
Finsterer, Josef
Scorza, Fulvio A. [UNIFESP]
Type
ArtigoISSN
0920-1211Is part of
Epilepsy ResearchDOI
10.1016/j.eplepsyres.2017.07.003Metadata
Show full item recordAbstract
Objectives: Antiepileptic drugs (AEDs) exhibit adverse and beneficial effects on mitochondria, which have a strong impact on the treatment of patients with a mitochondrial disorder (MID) with epilepsy (mitochondrial epilepsy). This review aims at summarizing and discussing recent findings concerning the effect of AEDs on mitochondrial functions and the clinical consequences with regard to therapy of mitochondrial epilepsy and of MIDs in general. Methods: Literature review. Results: AEDs may interfere with the respiratory chain, with non-respiratory chain enzymes, carrier proteins, or mitochondrial biogenesis, with carrier proteins, membrane-bound channels or receptors and the membrane potential, with anti-oxidative defense mechanisms, with morphology, dynamics and survival of mitochondria, and with the mtDNA. There are AEDs of which adverse effects outweigh beneficial effects, such as valproic acid, carbamazepine, phenytoin, or phenobarbital and there are AEDs in which beneficial effects dominate over mitochondrial toxic effects, such as lamotrigine, levetiracetam, gabapentin, or zonisamide. However, from most AEDs only little is known about their interference with mitochondria. Conclusions: Mitochondrial epilepsy might be initially treated with AEDs with low mitochondrial toxic potential. Only in case mitochondrial epilepsy is refractory to these AEDs, AEDs with higher mitochondrial toxic potential might be tried. In patients carrying POLG1 mutations AEDs with high mitochondrial toxic potential are contraindicated.
Citation
Epilepsy Research. Amsterdam, v. 136, p. 5-11, 2017.Keywords
side effectstoxicity
epilepsy
antiepileptic drugs
mitochondrion
reactive oxygen species
apoptosis
membrane potential
oxidative stress
respiratory chain
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