2019
A single‐center, open‐label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers
Finnema SJ, Rossano S, Naganawa M, Henry S, Gao H, Pracitto R, Maguire RP, Mercier J, Kervyn S, Nicolas J, Klitgaard H, DeBruyn S, Otoul C, Martin P, Muglia P, Matuskey D, Nabulsi NB, Huang Y, Kaminski RM, Hannestad J, Stockis A, Carson RE. A single‐center, open‐label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers. Epilepsia 2019, 60: 958-967. PMID: 30924924, PMCID: PMC6532410, DOI: 10.1111/epi.14701.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnticonvulsantsCarbon RadioisotopesFemaleHealthy VolunteersHumansInhibitory Concentration 50Injections, IntravenousLevetiracetamMagnetic Resonance ImagingMaleMembrane GlycoproteinsNerve Tissue ProteinsNeuroimagingPositron-Emission TomographyProtein BindingPyrrolidinonesConceptsSynaptic vesicle glycoprotein 2AIntravenous brivaracetamHours postdoseBrain penetrationHealthy volunteersDaily oral dosingPositron emission tomography studyFurther clinical studiesEmission tomography studiesPlasma concentration relationshipPositron emission tomography (PET) tracerEmission tomography tracerVivo animal studiesAcute seizuresAntiepileptic drugsTherapeutic dosesCohort 2Oral dosingCohort 1Clinical studiesCohort 3LevetiracetamAnimal studiesRelevant dosesBrivaracetam
2016
Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain
Nabulsi N, Mercier J, Holden D, Carré S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. Journal Of Nuclear Medicine 2016, 57: 777-784. PMID: 26848175, DOI: 10.2967/jnumed.115.168179.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AWhole-body biodistributionPET radiotracersNonhuman primatesDose-limiting organHigher free fractionGray matter regionsBaseline VTNondisplaceable distribution volumeAntiepileptic drugsVitro inhibition constantSynaptic densityPreclinical evaluationMonkey brainDistribution volumeArterial samplingEndocrine cellsRegional volumesMatter regionsRhesus macaquesPET tracersUCBFree fractionBrainTarget occupancy
2015
Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A, Mathy FX, Mercier J, Stockis A, Carson RE, Klitgaard H. Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 2015, 57: 201-209. PMID: 26663401, DOI: 10.1111/epi.13267.Peer-Reviewed Original ResearchConceptsFaster onsetAcute seizuresHigh-affinity synaptic vesicle protein 2A ligandNonhuman primate PET studyAudiogenic seizure miceRapid brain entryOnset of actionSingle oral dosingHigh brain permeabilityBlood-brain barrier permeability (BBBP) valuesPrimate PET studyAudiogenic miceBrain entryCaco-2 cellsSeizure micePreclinical evidenceAntiepileptic drugsSusceptible miceBrain levelsBrain penetrationPreclinical dataBrain kineticsOral dosingSingle dosingClinical studies