Narrative review of brivaracetam for genetic generalized epilepsies

Lince-Rivera, Isabella; Córdoba, Natalia; Rosa, Johann Sebastián Ortiz De la

doi:10.1016/j.seizure.2022.10.009

Search citation statements

Order By: Relevance

Paper Sections

Select...

Introduction1

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article2

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

(1 citation statement)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 11 In Europe, BRV was initially authorized as a supplementary therapy for focal onset seizures, whether with or without secondary generalization. 12 …”

Section: Introductionmentioning

confidence: 99%

A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study

Siddiqui,

Soomro,

Rehman

et al. 2024

DIC

View full text Add to dashboard Cite

“… 11 In Europe, BRV was initially authorized as a supplementary therapy for focal onset seizures, whether with or without secondary generalization. 12 …”

Section: Introductionmentioning

confidence: 99%

A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study

Siddiqui,

Soomro,

Rehman

et al. 2024

DIC

View full text Add to dashboard Cite

Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A

Yamagata,

Ito,

Suzuki

et al. 2024

Nat Commun

View full text Add to dashboard Cite

More than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. Synaptic vesicle glycoprotein 2a (SV2A), a putative membrane transporter in the synaptic vesicles (SVs), has been identified as a target of LEV and BRV. SV2A also serves as a receptor for botulinum neurotoxin (BoNT), which is the most toxic protein and has paradoxically emerged as a potent reagent for therapeutic and cosmetic applications. Nevertheless, no structural analysis on AEDs and BoNT recognition by full-length SV2A has been available. Here we describe the cryo-electron microscopy structures of the full-length SV2A in complex with the BoNT receptor-binding domain, BoNT/A2 HC, and either LEV or BRV. The large fourth luminal domain of SV2A binds to BoNT/A2 HC through protein-protein and protein-glycan interactions. LEV and BRV occupy the putative substrate-binding site in an outward-open conformation. A propyl group in BRV creates additional contacts with SV2A, explaining its higher binding affinity than that of LEV, which was further supported by label-free spectral shift assay. Numerous LEV derivatives have been developed as AEDs and positron emission tomography (PET) tracers for neuroimaging. Our work provides a structural framework for AEDs and BoNT recognition of SV2A and a blueprint for the rational design of additional AEDs and PET tracers.

show abstract

Narrative review of brivaracetam for genetic generalized epilepsies

Cited by 2 publications

References 39 publications

A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study

A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study

Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A

Contact Info

Product

Resources

About