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 studied electrophysiologically in a model of human absence seizures: rhythmic metrazol activity (RMA) in rats. The effects of Ro 16-6028 pretreatment (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 (VPA, 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 similar to those of CZP and VPA, i.e., suppression of RMA episodes, an increase in latency and a decrease in number, and total as well as mean duration. On the other hand, ESM differed from these antiepileptic drugs (AEDs) in inability to shorten the duration of RMA episodes. Based on these results, Ro 16-6028 might be predicted to be efficient against human absence seizures.
Brabcová
R
R
Institute of Physiology, Czechoslovak Academy of Sciences, Prague.
Kubová
H
H
Velísek
L
L
Mares
P
P
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000139:chemically induced* / Q000517:prevention & control; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D001570:Benzodiazepinones; D018079:Receptors, GABA; D002998:Clonazepam; D014635:Valproic Acid; C054626:bretazenil; D010433:Pentylenetetrazole