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Anticonvulsant Activity of Novel 1‐(Substituted Benzylidene)‐4‐(1‐(Morpholino/Piperidino Methyl)‐2,3‐Dioxoindolin‐5‐yl) Semicarbazide Derivatives in Mice and Rats Acute Seizure Models
Author(s) -
Prakash Chinnasamy Rajaram,
Raja Sundararajan,
Saravanan Govindaraj
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01399.x
Subject(s) - anticonvulsant , phenytoin , semicarbazide , pharmacology , neurotoxicity , chemistry , in vivo , epilepsy , medicine , toxicity , organic chemistry , biology , microbiology and biotechnology , psychiatry
A series of novel 1‐(substituted benzylidene)‐4‐(1‐(morpholino/piperidino methyl)‐2,3‐dioxoindolin‐5‐yl) semicarbazides 6a–6t was designed and synthesized on the basis of semicarbazide‐based pharmacophoric model to meet the structural requirements necessary for anticonvulsant activity. The compounds were subjected to in vivo antiepileptic evaluation using maximal electroshock test and subcutaneous pentylenetetrazole seizure test methods. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 6c, 6d, 6g, 6h, and 6m were found active in maximal electroshock test model, while 6g, 6i, 6m, and 6o showed significant antiepileptic activity in subcutaneous pentylenetetrazole seizure test model. Further, the compounds 6c, 6d, 6g, 6h, 6i, and 6m were administered orally to rats, of which 6c and 6g showed better activity than phenytoin. Among the synthesized compounds, 6g revealed excellent protection in both models with lower neurotoxicity.