ANTICONVULSANT PROPERTIES OF 1,4-BENZODIAZEPINE DERIVATIVES IN AMYGDALOID-KINDLED SEIZURES AND THEIR CHEMICAL STRUCTURE-RELATED ANTICONVULSANT ACTION

The effects of 14 different 1,4-benzodiazepines on amygdaloid-kindled seizures and their chemical structure-related anticonvulsive actions w ere studied. The prophylactic effects of 1,4-benzodiazepines on amygda loid-kindled seizures were also examined. Male Wistar strain rats were used in this study. Rats were anesthetized with pentobarbital sodium (35 mg/kg i.p.) and bipolar electrodes were implanted into the right a mygdala. The stimulating parameters were 1 ms pulse duration, 60 Hz fr equency and a I s duration at an intensity just sufficient to induce a fterdischarge (AD). All the 1,4-benzodiazepines depressed both seizure stage and AD duration of amygdaloid-kindled seizures. Of the 1,4-benz odiazepines, prazepam, flutoprazepam and flurazepam with a long alkyl chain at position 1 were less effective than the drugs having a hydrog en or methyl group at the same position. Nitrazepam, nimetazepam, flun itrazepam and clonazepam which have a nitro group at position 7 showed more potent antiepileptic activity than the drugs with a chloro group . Certain 1,4-benzodiazepines caused inhibition of the development of amygdaloid-kindled seizures. The existence of a hydrogen or methyl gro up at position 1 and a nitro group at position 7 is important for exhi biting potent anticonvulsant activity in amygdaloid-kindled seizures. Introduction of an oxygen group at position 2 is also necessary for hi gh activity. 1,4-benzodiazepines had not only therapeutic but also pro phylactic effects on amygdaloid-kindled seizures.