On the convulsant action of Ro 5-4864 and the existence of a micromolar benzodiazepine binding site in rat brain.

The benzodiazepine Ro 5-4864 (60 mg/kg) produced convulsions in mice that could be antagonised either by diazepam (2-4 mg/kg) or by Ro 15-1788 (10-20 mg/kg). In mice and rats subconvulsant doses of Ro 5-4864 were proconvulsant when combined with subconvulsant doses of picrotoxin or pentylenetetrazole. Ro 15-1788 antagonised the tonic convulsions triggered by the drug combinations when it was given at the same time as Ro 5-4864; this antagonism was not observed when the drugs were injected at different times. In contrast to a previous report, we could find no evidence that Ro 5-4864 antagonised seizures induced by electroshock. Using two different ligand-binding techniques, no evidence was seen for the existence in rat brain of the previously reported "micromolar" benzodiazepine receptor, a suggested site of action of Ro 5-4864.