Anticonvulsant and Sedative-Hypnotic Activities of N-Acetyl / Methyl Isatin Derivatives

A series of N-methyl/acetyl 5-(un)-substituted isatin-3-semicarbazones were screened for anticonvulsant and sedative-hypnotic activities. The results revealed that protection was obtained in all the screens i.e., Maximal electroshock, (MES) subcutaneous pentylene tetrazole (scPTZ) and subcutaneous strychnine (scSTY) screens. Three compounds (5a, 5e and 5i) possessed anti-MES activity and all the compounds were less neurotoxic than phenytoin, carbamazepine and phenobarbital. All the compounds were completely non-toxic at 4h when compared to phenytoin, carbamazepine and phenobarbital, which were toxic at 100 and 300 mg/kg respectively. Compounds 5a, 5b, 5e, 5g and 5i emerged as the active compounds in oral MES screen. Selected compounds were evaluated for quantification studies in MES, scPTZ and neurotoxicity screens after i. p (5b, 5i) and oral administration (5a, 5g) in rats. Among all the compounds 5a, 5b and 5g emerged as broad-spectrum compounds as indicated by their protection in MES, scSTY and scPTZ screens. All the compounds except compound 5b showed significant sedative-hypnotic activity.