Biphasic effects of Ro 15-1788 on spontaneous petit mal-like seizures in rats

The effects of various doses of the potent and specific benzodiazepine antagonist Ro 15-1788 were investigated in rats with spontaneous non convulsive, petit mal-like seizures. In preliminary experiments, Ro 15-1788, 2 mg/kg i.p., completely but transiently antagonized the antiepileptic action of diazepam, 2 mg/kg i.p. Ro 15-1788, 2 mg/kg, given alone, exhibited no intrinsic activity. At 10-80 mg/kg, it acted as an antiepileptic; this dose-dependent suppressant effect developed slowly over 20-40 min after injection and was never total even at 80 mg/kg. At the highest dose, Ro 15-1788 also had a transient epileptogenic effect immediately following the injection. These results confirm that Ro 15-1788 is not a pure benzodiazepine antagonist but also has partial 'agonist' and 'inverse agonist' properties.