Sci Pharm. 2008; 76: 621–636.
Anticonvulsant and Sedative-Hypnotic Activities of N-Acetyl / Methyl Isatin Derivatives
Sivakumar SMITHA * 1, Surendra N. PANDEYA 2 , James P. STABLES 3, Suthakar GANAPATHY 4
1 Department of Pharmaceutical Analysis, C.L.Baid Metha College of Pharmacy, Rajiv Gandhi Salai, Thorapakkam, Chennai 600 096, India.
2 Department of Pharmacy, Saroj Institute of Technology and Management, Arjunganj, Lucknow, 226 002, India.
3 National Institute of Neurological Disorders and Stroke, NIH, Maryland, 20892-9020, USA.
4 Department of Pathology, University of Texas Health Science Center at San Antonio, 7703, Floyd Curl Drive, San Antonio, Texas-78229, USA.
* Corresponding author. E-mail: firstname.lastname@example.org (S. Smitha).
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 (2a, 2e and 2i) 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 2a, 2b, 2e, 2g and 2i 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 (2b, 2i) and oral administration (2a, 2g) in rats. Among all the compounds 2a, 2b and 2g emerged as broad-spectrum compounds as indicated by their protection in MES, scSTY and scPTZ screens. All the compounds except compound 2b showed significant sedative-hypnotic activity.
Isatin-3-semicarbazones • Anticonvulsant • Maximal electroshock • Sedative-hypnotic
Received June 30th, 2008 | Accepted September 14th, 2008 | Published Online September 17th, 2008