Synthesis and anticonvulsant activity of two N-(2,6-dimethylphenyl)pyridinedicarboximides

Two N-(2,6-dimethylphenyl)pyridinedicarboximides were synthesized and evaluated for anticonvulsant properties and neurotoxicity. These compounds were mainly active against maximal electroshock (MES) induced seizures in animal models. In rats dosed orally, N-(2,6-dimethylphenyl-2,3-pyridinedicarboximide 1 exhibited an anti-MES ED50 of 54.2 μmol/kg and a protective index (PI = TD50/ED50) superior to 27.4. In mice dosed intraperitoneally, compound 1 is less active against MES induced seisure (ED50 = 160.9 μmol/kg) and more neurotoxic as evidenced by a low protective index (1.93). Comparison with published data on phenytoin reveals that compound 1 is, in rats dosed orally, two-fold more potent than this antiepileptic drug against MES induced seizures.