Abstract

In the present study on the development of new anticonvulsants, twenty new 6-methyl-1-substituted-4,6-diazaspiro[2.4]heptane-5,7-diones were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole ( scPTZ) screens. Their neurotoxicity was determined by the rotorod test. In this series, all of the alkyl- and aryl-substituted 5,5-cyclopropanespirohydantoins showed more or less protection against MES and/or scPTZ models. The most active of the series was 6-methyl-1-(4-(methylsulfonyl)phenyl)-4,6-diazaspiro[2.4]heptane-5,7-dione ( 6t), which showed a MES ED 50 value of 12.5 mg/kg in mice. The median toxic dose (TD 50) was 310 mg/kg, providing compound 6t with a protection index (PI = TD 50/ED 50) of 24.8 in the MES test which is better than phenytoin.

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