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Updated: Oct 18, 2025
Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
Selected Molecular Targets for Antiepileptogenesis
Marek J Pawlik1, Barbara Miziak2, Aleksandra Walczak2
1Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Abstract:
The term epileptogenesis defines the usually durable process of converting normal brain into an epileptic one. The resistance of a significant proportion of patients with epilepsy to the available pharmacotherapy prompted the concept of a causative treatment option consisting in stopping or modifying the progress of epileptogenesis. Most antiepileptic drugs possess only a weak or no antiepileptogenic potential at all, but a few of them appear promising in this regard; these include, for example, eslicarbazepine (a sodium and T-type channel blocker), lamotrigine (a sodium channel blocker and glutamate antagonist) or levetiracetam (a ligand of synaptic vehicle protein SV2A). Among the approved non-antiepileptic drugs, antiepileptogenic potential seems to reside in losartan (a blocker of angiotensin II type 1 receptors), biperiden (an antiparkinsonian drug), nonsteroidal anti-inflammatory drugs, antioxidative drugs and minocycline (a second-generation tetracycline with anti-inflammatory and antioxidant properties). Among other possible antiepileptogenic compounds, antisense nucleotides have been considered, among these an antagomir targeting microRNA-134. The drugs and agents mentioned above have been evaluated in post-status epilepticus models of epileptogenesis, so their preventive efficacy must be verified. Limited clinical data indicate that biperiden in patients with brain injuries is well-tolerated and seems to reduce the incidence of post-traumatic epilepsy. Exceptionally, in this regard, our own original data presented here point to c-Fos as an early seizure duration, but not seizure intensity-related, marker of early epileptogenesis. Further research of reliable markers of early epileptogenesis is definitely needed to improve the process of designing adequate antiepileptogenic therapies.
Insights
Developing new treatments for epilepsy is crucial as many patients resist current drugs. Research explores compounds like eslicarbazepine and biperiden for their potential to stop epileptogenesis, the process of developing epilepsy.
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Epileptogenesis is the process of normal brain developing into an epileptic one.
- Drug resistance in epilepsy necessitates the development of causative treatments targeting epileptogenesis.
- Current antiepileptic drugs often lack significant antiepileptogenic potential.
Purpose of the Study:
- To review existing and potential antiepileptogenic therapies.
- To identify compounds with the potential to halt or modify epileptogenesis.
- To highlight the need for further research into early epileptogenesis markers and therapies.
Main Methods:
- Review of existing literature on antiepileptogenic drugs and agents.
- Evaluation of compounds including eslicarbazepine, lamotrigine, levetiracetam, losartan, and biperiden.
- Analysis of preclinical models and limited clinical data for antiepileptogenic efficacy.
- Investigation of c-Fos as a potential early marker of epileptogenesis.
Main Results:
- Several drugs, including eslicarbazepine, lamotrigine, and levetiracetam, show promise as antiepileptogenic agents.
- Non-antiepileptic drugs like losartan, biperiden, NSAIDs, and minocycline also exhibit antiepileptogenic potential.
- Biperiden appears well-tolerated in patients with brain injuries and may reduce post-traumatic epilepsy incidence.
- c-Fos is identified as an early marker related to seizure duration, not intensity, in epileptogenesis.
Conclusions:
- A range of pharmacological agents, both antiepileptic and non-antiepileptic, are being investigated for their antiepileptogenic properties.
- Preventive efficacy of these agents requires further verification in relevant models and clinical trials.
- Identification of reliable early epileptogenesis markers, such as c-Fos, is essential for developing effective antiepileptogenic therapies.
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