Synthesis and anticonvulsant activity of new phenytoin derivatives.

Hybrids between phenytoin and thiosemicarbazide, 1,3,4-oxadiazole, 1,3,4-thiadiazole or 1,2,4-triazole were synthesized and tested for anticonvulsant activity. Preliminary anticonvulsant screening was performed using standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens in mice. The neurotoxicity was determined applying the rotarod test. Among these compounds, 4 and 5d showed the highest protection (80%) in the scPTZ test at a dose of 100 mg/kg, whereas the compound 5b displayed promising anticonvulsant effect in the MES model.