Antiseizure drug efficacy and tolerability in established and novel drug discovery seizure models in outbred vs inbred mice.

ABSTRACT:

Objective

Initial identification of new investigational drugs for the treatment of epilepsy is commonly conducted in well-established mouse acute and chronic seizure models: for example, maximal electroshock (MES), 6 Hz, and corneal kindling. Comparison of the median effective dose (ED50) of approved antiseizure drugs (ASDs) vs investigational agents in these models provides evidence of their potential for clinical efficacy. Inbred and outbred mouse strains exhibit differential seizure susceptibility. However, few comparisons exist of the ED50 or median behaviorally impairing dose (TD50) of prototype ASDs in these models in inbred C57Bl/6 vs outbred CF-1 mice, both of which are often used for ASD discovery.

Methods

We defined the strain-related ED50s and TD50s of several mec

SUBMITTER: Koneval Z 

PROVIDER: S-EPMC7722177 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature