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.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004597:Electroshock; D005442:Flumazenil; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis*; D011963:Receptors, GABA-A; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control
D001570:Benzodiazepinones; D003292:Convulsants; D003975:Diazepam; D005442:Flumazenil; D010433:Pentylenetetrazole; D010852:Picrotoxin; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam