Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 35, Issue 10, Pages 879-886Publisher
EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/S0223-5234(00)01169-7
Keywords
semicarbazones; electroshock; pentylenetetrazole; strychnine; neurotoxicity; pentobarbitone
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A number of 4-bromophenyl semicarbazones were synthesised and evaluated for anticonvulsant and sedative-hypnotic activities. After intraperitoneal injection to mice, the semicarbazone derivatives were examined in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY) and neurotoxicity (NT) screens. All the compounds showed anticonvulsant activity in one or more test models. Compound 12 showed greatest activity, being active in all the screens with very low neurotoxicity and no sedative-hypnotic activity. All the compounds except 7 had lower neurotoxicity compared to phenytoin. Three compounds (6, 11 and 14) showed greater protection than sodium valproate. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
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