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Chandra Bhushan Mishra,Shikha Kumari,Manisha Tiwari 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.5
A series of 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-urea derivatives (29–42) weredesigned, synthesized and evaluated for their anticonvulsantactivity by using maximal electroshock (MES), subcutaneouspentylenetetrazole (scPTZ) seizure tests. Theacute neurotoxicity was checked by rotarod assay. Most ofthe test compounds were found effective in both seizuretests. Compound 30 (1-{4-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3-phenyl-urea) exhibited marked anticonvulsantactivity in MES as well as scPTZ tests. The phaseII anticonvulsant quantification study of compound 30indicates the ED50 value of 28.5 mg/kg against MESinduced seizures. In addition, this compound also showedconsiderable protection against pilocarpine induced statusepilepticus in rats. Seizures induced by 3-mercaptopropionicacid model and thiosemicarbazide were significantlyattenuated by compound 30, which suggested its broadspectrum of anticonvulsant activity. Interestingly, compound30 displayed better antidepressant activity thanstandard drug fluoxetine. Moreover, compound 30appeared as a non-toxic chemical entity in sub-acute toxicitystudies.
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