In the present series of experiments, effects of a full
benzodiazepine receptor agonist (
diazepam) are described and compared with those of a partial
benzodiazepine receptor agonist (
ZK 91296) and an inverse partial
benzodiazepine receptor agonist (
FG 7142), both compounds of the
beta-carboline family. In a rat model for generalized
absence epilepsy, the
anticonvulsant, the
hypnotic and the myorelaxant properties were investigated, as well as effects on on-going behavior and effects on the electroencephalogram (EEG). While
diazepam showed all behavioral and electrophysiological changes characteristic for the
benzodiazepines, the partial agonist
ZK 91296 reduced seizure activity without inducing any signs of sedation,
sleepiness, myorelaxation and changes in behavior or EEG spectral content. The partial inverse agonist
FG 7142 aggrevated epileptic activity, with slightly enhanced immobile behavior, suggesting some anxiogenic properties. The results not only demonstrate that the multiple effects of the
benzodiazepines could be separated by these compounds, but also that the
anticonvulsant activity is not related to changes in spectral content of the EEG. Because of its selective activity,
ZK 91296 appears to be more suitable than
diazepam in reducing seizure activity. Finally,
FG 7142 seems a genuine partial inverse agonist which has some, but not all, of the inverse effects of a full agonist.