In our current study, we developed a focused series of original ((benzyloxy)benzyl)propanamide derivatives that demonstrated potent activity across in vivo mouse seizure models, specifically, maximal electroshock (MES) and 6 Hz (32 mA) seizures. Among these derivatives, compound emerged as a lead molecule, exhibiting robust protection following intraperitoneal (i.p.) injection, as follows: ED = 48.0 mg/kg in the MES test, ED = 45.2 mg/kg in the 6 Hz (32 mA) test, and ED = 201.3 mg/kg in the 6 Hz (44 mA) model. Additionally, compound displayed low potential for inducing motor impairment in the rotarod test (TD > 300 mg/kg), indicating a potentially favorable therapeutic window. In vitro toxicity assays further supported its promising safety profile. We also attempted to identify a plausible mechanism of action of compound by applying both binding and functional in vitro studies. Overall, the data obtained for this lead molecule justifies the more comprehensive preclinical development of compound as a candidate for a potentially broad-spectrum and safe anticonvulsant.
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| http://dx.doi.org/10.3390/ijms25189861 | DOI Listing |
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