Discovery and Profiling of New Multimodal Phenylglycinamide Derivatives as Potent Antiseizure and Antinociceptive Drug Candidates.

ABSTRACT: We developed a focused series of original phenyl-glycinamide derivatives which showed potent activity across in vivo mouse seizure models, namely, maximal electroshock (MES) and 6 Hz (using both 32 and 44 mA current intensities) seizure models. Following intraperitoneal (i.p.) administration, compound (R)-32, which was identified as a lead molecule, demonstrated potent protection against all seizure models with ED₅₀ values of 73.9 mg/kg (MES test), 18.8 mg/kg (6 Hz, 32 mA test), and 26.5 mg/kg (6 Hz, 44 mA test). Furthermore, (R)-32 demonstrated efficacy in both the PTZ-induced kindling paradigm and the ivPTZ seizure threshold test. The expression of neurotrophic factors, such as mature brain-derived ne

SUBMITTER: Jakubiec M 

PROVIDER: S-EPMC11378297 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature