EFFECTS OF A BENZODIAZEPINE, BRETAZENIL (RO-16-6028), ON RHYTHMIC METRAZOL EEG ACTIVITY - COMPARISON WITH STANDARD ANTICONVULSANTS

A novel anticonvulsant benzodiazepine bretazenil (Ro 16-6028) was stud ied electrophysiologically in a model of human absence seizures: rhyth mic metrazol activity (RMA) in rats. The effects of Ro 16-6028 pretrea tment (0.01, 0.05, or 0.1 mg/kg intraperitoneally, i.p.) were compared with those of clonazepam (CZP, 0.02 or 0.1 mg/kg i.p.), valproate (VP A, 200, 300, or 400 mg/kg) and ethosuximide (ESM, 31.25, 62.5, or 125 mg/kg i.p.) in 45 rats with implanted electrocorticographic electrodes . RMA was elicited by an injection of pentylenetetrazol (metrazol, PTZ ) in a dose of 40 or 35 mg/kg i.p. The effects of Ro 16-6028 were simi lar to those of CZP and VPA, i.e., suppression of RMA episodes, an inc rease in latency and a decrease in number, and total as well as mean d uration. On the other hand, ESM differed from these antiepileptic drug s (AEDs) in inability to shorten the duration of RMA episodes. Based o n these results, Ro 16-6028 might be predicted to be efficient against human absence seizures.