Anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin derivatives.
In the present study, anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin were evaluated by maximal electroshock method (MES) and metrazol-induced convulsions (MET) at 30, 100 and 300 mg/kg dose levels. Neurotoxicity of the compounds was also assessed at the same dose levels. Eight compounds of the series exhibited significant anticonvulsant activity at 30 mg/kg dose level. 3-(4-chloro-phenylimino)-5-methyl-1,3-dihydro-indol-2-one (compound 10) was found to be the most potent compound of the series with 87% protection at 100 mg/kg and an ED(50) of 53.61 mg/kg (MET). All the compounds exhibited lesser neurotoxicity compared to phenytoin. All the active compounds showed greater protection than sodium valproate. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore.
Department of Pesticide Chemistry, Fredrick Institute of Plant Protection and Toxicology, Padappai, 601301, India.
Seshaiah Krishnan
SK
Sridhar
Surendra N
SN
Pandeya
James P
JP
Stables
Atmakuru
A
Ramesh
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D004597:Electroshock / Q000379:methods; D006835:Hydrazones / Q000737:chemistry* / Q000494:pharmacology; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008352:Mannich Bases / Q000737:chemistry; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012545:Schiff Bases / Q000737:chemistry
D000927:Anticonvulsants; D006835:Hydrazones; D008352:Mannich Bases; D012545:Schiff Bases; D007510:Isatin