Novel test strategies for in vitro seizure liability assessment.

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 or 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 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 and 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 situation and increase their predictive value.