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 mumol/kg and a protective index (PI = TD50/ED50) superior to 27.4. In mice dosed intraperitoneally, compound 1 is less active against MES induced seizure (ED50 = 160.9 mumol/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.
Bailleux
V
V
Epilepsy Center/Pediatric Neurology, Centre Hospitalier Universitaire de Lille, Hôpital B, France.
Vallée
L
L
Nuyts
J P
JP
Vamecq
J
J
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009498:Neurotoxins / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; C094598:N-(2,6-dimethylphenyl)-3,4-pyridinedicarboximide; D009498:Neurotoxins; D011725:Pyridines; C094596:N-(2,6-dimethylphenyl)-2,3-pyridinedicarboximide