Novel test strategies for in vitro seizure liability assessment

Anke M Tukker, Remco H S Westerink

Research output: Contribution to journalReview articlepeer-review


INTRODUCTION: The increasing incidence of mental illnesses and neurodegenerative diseases results in a high demand for drugs targeting the central nervous system (CNS). These drugs easily reach the CNS, have a high affinity for CNS targets, and are prone to cause seizures as an adverse drug reaction. Current seizure liability assessment heavily depends on in vivo or ex vivo animal models and is therefore ethically debated, labor intensive, expensive, and not always predictive for human risk.

AREAS COVERED: The demand for CNS drugs urges the development of alternative safety assessment strategies. Yet, the complexity of the CNS hampers reliable detection of compound-induced seizures. This review provides an overview of the requirements of in vitro seizure liability assays and highlights recent advances, including micro-electrode array (MEA) recordings using rodent and human cell models.

EXPERT OPINION: Successful and cost-effective replacement of in vivo and ex vivo models for seizure liability screening can reduce animal use for drug development, while increasing the predictive value of the assays, particularly if human cell models are used. However, these novel test strategies require further validation and standardization as well as additional refinements to better mimic the human in vivo situation and increase their predictive value.

Original languageEnglish
Pages (from-to)923-936
Number of pages14
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number8
Early online date17 Feb 2021
Publication statusPublished - 2021


  • Alternatives to animal testing
  • GABA receptor antagonists
  • drug safety assessment
  • human-induced pluripotent stem cell (hiPSC)-derived neuronal models
  • in vitro seizure liability assessment
  • ion channels
  • micro-electrode array (MEA) recordings
  • rodent primary cortical cultures
  • safety pharmacology


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