In vitro human ion channel assays predictive of drug-induced seizure.

ABSTRACT: Seizure is among the most severe FDA black box warnings of neurotoxicity reported on drug labels. Gaining a better mechanistic understanding of off-targets causative of seizure will improve the identification of potential seizure risks preclinically. In the present study, we evaluated an in vitro panel of 9 investigational (Cav2.1, Cav3.2, GlyRA1, AMPA, HCN1, Kv1.1, Kv7.2/7.3, NaV1.1, Nav1.2) and 2 standard (GABA-A, NMDA) ion channel targets with strong correlative links to seizure, using automated electrophysiology. Each target was assessed with a library of 34 preclinical compounds and 10 approved drugs with known effects of convulsion in vivo and/or in patients. Cav2.1 had the highest frequency of positive hits, 20 compounds with an EC30 or IC30 ≤ 30 µM, and the highest importance score

SUBMITTER: Cohen JD 

PROVIDER: S-EPMC11775423 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature