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Updated: Nov 13, 2025
Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
Two decades of research towards a potential first anti-epileptic drug
Simone Kastropil Benassi1, Julieta Goncalves Silva Macedo Alves1, Cristiane Gorgatti Guidoreni1
1Physiology Department, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Abstract:
The basic mechanisms by which brain insults, such as trauma, stroke or status epilepticus produce epilepsy are not completely understood, and effective preventive measures and treatment are still not available in the clinical setting. Over the last 2 decades we have conducted several studies with animal models of epilepsy (rodents and non-human primates) and demonstrated that drugs that modify neuronal plastic processes, such as anticholinergic agents (e.g., antimuscarinic compounds), if administered soon after brain injury and over a period of 10-20 days, have the potential to modify the natural course of post-traumatic epilepsy. To that end treatment with scopolamine showed promising results as a candidate agent in both the pilocarpine and kainate models. We then showed that biperiden, yet another cholinergic antagonist acting in the muscarinic receptor, that is widely used to treat Parkinson's disease, also decreased the incidence and intensity of spontaneous epileptic seizures, delaying their appearance in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as an antiepileptogenic agent. Accordingly, we tested the safety of biperiden in a small group of patients (as a small phase II safety assessment) and confirmed its safety in the context of traumatic brain injury (TBI). Now, we provide information on our ongoing project to evaluate the efficacy of biperiden in preventing the development of epilepsy in patients that suffered TBI, in a double blind, randomized, placebo-controlled trial.
Insights
Biperiden, an anticholinergic drug, may prevent epilepsy after brain injury. Clinical trials are underway to confirm its efficacy in patients with traumatic brain injury (TBI).
Area of Science:
- Neuroscience
- Pharmacology
- Epileptology
Background:
- Epilepsy mechanisms post-brain injury remain unclear, lacking effective preventive treatments.
- Anticholinergic drugs targeting neuronal plasticity show potential in animal models.
- Biperiden, a muscarinic receptor antagonist, demonstrated antiepileptogenic properties in preclinical studies.
Purpose of the Study:
- To evaluate the efficacy of biperiden in preventing epilepsy following traumatic brain injury (TBI).
- To build upon promising preclinical findings with scopolamine and biperiden in epilepsy models.
- To assess biperiden's safety and potential as an antiepileptogenic agent in TBI patients.
Main Methods:
- Preclinical studies using rodent and non-human primate models of epilepsy.
- Administration of anticholinergic agents like scopolamine and biperiden post-brain injury.
- Phase II safety assessment of biperiden in traumatic brain injury patients.
- Ongoing double-blind, randomized, placebo-controlled trial to assess biperiden's efficacy in TBI patients.
Main Results:
- Scopolamine and biperiden demonstrated promising results in animal models of epilepsy.
- Biperiden reduced seizure incidence, intensity, and delayed onset in the pilocarpine model.
- Biperiden was confirmed safe in a small group of traumatic brain injury patients.
Conclusions:
- Biperiden shows potential as an antiepileptogenic agent for preventing post-traumatic epilepsy.
- Further clinical investigation is warranted to establish biperiden's efficacy in TBI patients.
- This ongoing trial aims to provide crucial data on biperiden's therapeutic role in epilepsy prevention.
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