Toxicol Appl Pharmacol 2021 Sep 15:115725. Epub 2021 Sep 15.
Department of Gene Tox and In Vitro Cellular Toxicology, Safety Assessment & Laboratory Animal Resources (SALAR), Merck & Co., Inc., West Point, PA 19486, USA.
An effective in vitro screening assay to detect seizure liability in preclinical development can contribute to better lead molecule optimization prior to candidate selection, providing higher throughput and overcoming potential brain exposure limitations in animal studies. This study explored effects of 26 positive and 14 negative reference pharmacological agents acting through different mechanisms, including 18 reference agents acting on glutamate signaling pathways, in a brain slice assay (BSA) of adult rat to define the assay's sensitivity, specificity, and limitations. Evoked population spikes (PS) were recorded from CA1 pyramidal neurons of hippocampus (HPC) in the BSA. Read More