Sridhar Seshaiah Krishnan, Pandeya Surendra N, Stables James P, Ramesh Atmakuru
Department of Pesticide Chemistry, Fredrick Institute of Plant Protection and Toxicology, Padappai, 601301, India.
Eur J Pharm Sci. 2002 Aug;16(3):129-32. doi: 10.1016/s0928-0987(02)00077-5.
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.
在本研究中,通过最大电休克法(MES)和戊四氮诱导惊厥法(MET),在30、100和300mg/kg剂量水平下评估了异吲哚酮腙、席夫碱和曼尼希碱的抗惊厥活性。还在相同剂量水平下评估了这些化合物的神经毒性。该系列中的8种化合物在30mg/kg剂量水平下表现出显著的抗惊厥活性。3-(4-氯苯基亚氨基)-5-甲基-1,3-二氢吲哚-2-酮(化合物10)被发现是该系列中最有效的化合物,在100mg/kg时具有87%的保护率,ED(50)为53.61mg/kg(MET)。与苯妥英相比,所有化合物的神经毒性均较小。所有活性化合物均显示出比丙戊酸钠更强的保护作用。在一个建议的药效团内确定了与受体位点相互作用的基本结构特征。