Differentiation of drug-induced rhythmical activities in the rabbit's brain by a benzodiazepine antagonist.

The effect of a benzodiazepine antagonist, ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788), on the cerebello-rubral rhythm induced by a water soluble benzodiazepine derivative (medazepam hydrochloride) or by a barbiturate (pentobarbital sodium) was investigated in the rabbit. The frequency of this rhythm which depends on the depth of the central depression caused by either of these agents was used for the drug interaction study. Ro 15-1788 when given alone up to 10 mg/kg did not cause any changes in the cerebello-rubral and the neocortical electrical activities. Ro 15-1788 (0.5 and 2.0 mg/kg) was effective in antagonizing the medazepam-induced cerebello-rubral rhythm and the rhythmic discharges of Purkinje cells in a dose-dependent manner. The antagonistic effect was also observed in the electrocorticogram. The pentobarbital-induced cerebello-rubral rhythm and the neocortical activity were not influenced by Ro 15-1788 up to 5 mg/kg. Thus, the similar effect of barbiturates and benzodiazepine derivatives on the cerebello-rubral system seems to be mediated by different pharmacodynamic actions. The findings are in line with previous studies indicating a selective antagonism of Ro 15-1788 and benzodiazepine derivatives.