T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures

Abstract

Absence seizures are a common seizure type in children with genetic generalized epilepsy and are characterized by a temporary loss of awareness, arrest of physical activity, and accompanying spike-and-wave discharges on an electroencephalogram. They arise from abnormal, hypersynchronous neuronal firing in brain thalamocortical circuits. Currently available therapeutic agents are only partially effective and act on multiple molecular targets, including γ-aminobutyric acid (GABA) transaminase, sodium channels, and calcium (Ca 2+) channels. We sought to develop high-affinity T-type specific Ca 2+ channel antagonists and to assess their efficacy against absence seizures in the Genetic Absence Ep..