Pronounced antiseizure activity of the subtype-selective GABA_A positive allosteric modulator darigabat in a mouse model of drug-resistant focal epilepsy.

ABSTRACT:

Aim

Darigabat is an α2/3/5 subunit-selective positive allosteric modulator of GABA_A receptors that has demonstrated broad-spectrum activity in several preclinical models of epilepsy as well as in a clinical photoepilepsy trial. The objective here was to assess the acute antiseizure effect of darigabat in the mesial temporal lobe epilepsy (MTLE) mouse model of drug-resistant focal seizures.

Methods

The MTLE model is generated by single unilateral intrahippocampal injection of low dose (1 nmole) kainic acid in adult mice, and subsequent epileptiform activity is recorded following implantation of a bipolar electrode under general anesthesia. After a period of epileptogenesis (~4 weeks), spontaneous and recurrent hippocampal paroxysmal discharges (HPD; focal seizures)

SUBMITTER: Gurrell R 

PROVIDER: S-EPMC9532903 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature