Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the\npharmacotoxicological profile.We herein tested its fluorinated and chlorinated derivatives (F-HEPP andCl-HEPP) with two seizure\nmodels, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was\nexamined via the rotarod test.With in silico methods, binding was probed on possible protein targetsââ?¬â?GABAA receptors and the\nsodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6,\n87.1, and 62.0mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5mg/kg. The HEPP-induced neurotoxic effect,\nwhich occurred at twice the ED50 against MES (
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