The effect of ML297 in vivo was investigated in several different behavioral assays, including those for epilepsy, anxiety, and insomnia (Figure 3). ML297 (60 mg/kg i.p.) exhibited improved efficacy compared to the anticonvulsant sodium valproate in both an electroshock and a pentylenetetrazol-induced mouse model of epilepsy, increasing the latency of seizure onset and preventing convulsions and lethality [25]. Huang and collaborators further demonstrated the antiepileptic effect of ML297 (30 mg/kg i.p.) [27]. ML297 diminished cyclothiazide-induced enhancement of neuronal excitability in cultured hippocampal neurons (Table 1), and reduced Racine score and extended seizure latency in a pilocarpine-induced mouse model of epilepsy [27]. In the elevated plus maze (EPM), ML297 (30 mg/kg i.p.) effectively reduced anxiety-like behavior in mice, and reduced stress-induced hyperthermia (Figure 3) [26]. These effects were absent in GIRK1 KO mice, implicating the action of ML297 on GIRK1-containing channels [26]. Moreover, ML297 did not affect locomotor activity in the open-field test, and did not show significant reinforcing effects in the conditioned place preference test at the studied dose (30 mg/kg i.p.). This suggested that the anxiolytic effects were not
