Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil

Wu, Peng-Peng; Cao, Bi-Rong; Tian, Fu-Yun; Gao, Zhao-Bing

doi:10.1007/s12264-023-01138-2

Cited by 9 publications

(8 citation statements)

References 141 publications

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“…BRV acts through selective affinity to synaptic vesicle glycoprotein 2A (SV2A) and blocks voltage-dependent sodium channels in neurons [ 65 , 67 ]. It has been approved for use in monotherapy or adjunctive therapy in children aged 1 month and older in the USA and as adjunctive therapy in children aged 2 years and older in the EU [ 70 , 71 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…Brivaracetam (BRV) is classified as a third-generation ASD [ 64 ]. It was approved by the FDA and EMA in 2016 [ 65 ]. In terms of structure, it belongs to the 4-n-propyl analogue of levetiracetam (LEV) [ 50 ].…”

Section: Pharmacological Agentsmentioning

confidence: 99%

“…The substance’s mechanism lies in its high and selective affinity for synaptic vesicle glycoprotein 2A (SV2A), which is as much as 15–30 times higher compared to LEV. SV2A is among the transmembrane glycoproteins found at glutamatergic and GABAergic synaptic terminals, and thus has implications for neuromodulation and neurotransmission [ 65 ]. The protein regulates the release and reuptake of neurotransmitters, which allows a decrease in neuronal excitability in the brain, which is desirable in epilepsy therapy [ 66 ].…”

Section: Pharmacological Agentsmentioning

confidence: 99%

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New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

Daniłowska,

Picheta,

Żyła

et al. 2024

JCM

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Epilepsy is a disorder characterized by abnormal brain neuron activity, predisposing individuals to seizures. The International League Against Epilepsy (ILAE) categorizes epilepsy into the following groups: focal, generalized, generalized and focal, and unknown. Infants are the most vulnerable pediatric group to the condition, with the cause of epilepsy development being attributed to congenital brain developmental defects, white matter damage, intraventricular hemorrhage, perinatal hypoxic-ischemic injury, perinatal stroke, or genetic factors such as mutations in the Sodium Channel Protein Type 1 Subunit Alpha (SCN1A) gene. Due to the risks associated with this condition, we have investigated how the latest pharmacological treatments for epilepsy in children impact the reduction or complete elimination of seizures. We reviewed literature from 2018 to 2024, focusing on the age group from 1 month to 18 years old, with some studies including this age group as well as older individuals. The significance of this review is to present and compile research findings on the latest antiseizure drugs (ASDs), their effectiveness, dosing, and adverse effects in the pediatric population, which can contribute to selecting the best drug for a particular patient. The medications described in this review have shown significant efficacy and safety in the studied patient group, outweighing the observed adverse effects. The main aim of this review is to provide a comprehensive summary of the current state of knowledge regarding the newest pharmacotherapy for childhood epilepsy.

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Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Agentsmentioning

confidence: 99%

Section: Pharmacological Agentsmentioning

confidence: 99%

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New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

Daniłowska,

Picheta,

Żyła

et al. 2024

JCM

View full text Add to dashboard Cite

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“…Synaptic vesicle protein 2A (SV2A), a transmembrane protein of synaptic vesicles implicated in the regulation of neurotransmitter release, acts as an important target of levetiracetam for the treatment of generalized epilepsy. Further, it was decreased in epileptic tissues and may even be correlated with the clinical efficacy of levetiracetam 4,5 . SV2A expression was downregulated by 30% in the hippocampus and temporal cortex of patients with pharmacoresistant temporal lobe epilepsy with hippocampal sclerosis 6 .…”

Section: Introductionmentioning

confidence: 98%

“…Further, it was decreased in epileptic tissues and may even be correlated with the clinical efficacy of levetiracetam. 4,5 SV2A expression was downregulated by 30% in the hippocampus and temporal cortex of patients with pharmacoresistant temporal lobe epilepsy with hippocampal sclerosis. 6 In some neurodegenerative and psychiatric disorders, SV2A was reduced 7,8 and SV2A loss was related to low synaptic density and brain atrophy.…”

mentioning

confidence: 94%

Synaptic vesicle protein 2A mitigates parthanatos via apoptosis‐inducing factor in a rat model of pharmacoresistant epilepsy

Li,

Wang,

Ren

et al. 2024

CNS Neurosci Ther

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AimsSynaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure‐induced neuronal programmed death, parthanatos was rarely reported in PRE. Apoptosis‐inducing factor (AIF), which has been implicated in parthanatos, shares a common cytoprotective function with SV2A. We aimed to investigate whether parthanatos participates in PRE and is mitigated by SV2A via AIF.MethodsAn intraperitoneal injection of lithium chloride‐pilocarpine was used to establish an epileptic rat model, and phenytoin and phenobarbital sodium were utilized to select PRE and pharmacosensitive rats. The expression of SV2A was manipulated via lentivirus delivery into the hippocampus. Video surveillance was used to assess epileptic ethology. Biochemical tests were employed to test hippocampal tissues following a successful SV2A infection. Molecular dynamic calculations were used to simulate the interaction between SV2A and AIF.ResultsParthanatos core index, PARP1, PAR, nuclear AIF and MIF, γ‐H2AX, and TUNEL staining were all increased in PRE. SV2A is bound to AIF to form a stable complex, successfully inhibiting AIF and MIF nuclear translocation and parthanatos and consequently mitigating spontaneous recurrent seizures in PRE. Moreover, parthanatos deteriorated after the SV2A reduction.SignificanceSV2A protected hippocampal neurons and mitigated epileptic seizures by inhibiting parthanatos via binding to AIF in PRE.

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Novel Mechanism, Drug Target and Therapy in Epilepsy

Xu,

Wang,

Chen

2024

Neurosci. Bull.

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Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil

Cited by 9 publications

References 141 publications

New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

Synaptic vesicle protein 2A mitigates parthanatos via apoptosis‐inducing factor in a rat model of pharmacoresistant epilepsy

Novel Mechanism, Drug Target and Therapy in Epilepsy

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