Approaches to seizure risk assessment in preclinical drug discovery.
Assessment of seizure risk traditionally occurs late in the drug discovery process using low-throughput, resource intensive in vivo assays. Such approaches do not allow sufficient time to mitigate risk by influencing chemical design. Early identification using cheaper, higher throughput assays with lower animal and compound requirements would be preferable. Here we review the current techniques available to assess this issue and describe how they may be combined in a rational step-wise cascade allowing more effective assessment of seizure risk.
Easter
Alison
A
Safety Assessment US, AstraZeneca R&D Wilmington, DE 19850, USA. Alison.Easter@astrazeneca.com
Bell
M Elizabeth
ME
Damewood
James R
JR
Redfern
William S
WS
Valentin
Jean-Pierre
JP
Winter
Matthew J
MJ
Fonck
Carlos
C
Bialecki
Russell A
RA
D000818:Animals; D019985:Benchmarking / Q000379:methods; D001921:Brain / Q000187:drug effects; D003198:Computer Simulation; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004594:Electrophysiology; D006801:Humans; D018570:Risk Assessment / Q000379:methods*; D012640:Seizures / Q000139:chemically induced*