Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo
Goodchild S, Shuart N, Williams A, Ye W, Parrish R, Soriano M, Thouta S, Mezeyova J, Waldbrook M, Dean R, Focken T, Ghovanloo M, Ruben P, Scott F, Cohen C, Empfield J, Johnson J. Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo. ACS Chemical Neuroscience 2024, 15: 1169-1184. PMID: 38359277, PMCID: PMC10958515, DOI: 10.1021/acschemneuro.3c00757.Peer-Reviewed Original ResearchExcitatory pyramidal neuronsPyramidal neuronsNeuronal action potential firingSeizure modelsActivity of excitatory neuronsInhibition of firingAction potential firingVoltage-gated sodium channelsSuppress epileptiform activityTherapeutic safety marginActivity ex vivoNeuronal hyperexcitabilityInhibitory interneuronsChannel inhibitorsEpileptiform activityInhibitory neuronsPotential firingExcitatory neuronsAntiseizure medicationsExcitatory circuitsBrain slicesReduced excitabilityPharmacological dissectionAntiseizure medication carbamazepineSodium channels