ro-5-3663 and pipequaline

1. The effects of some drugs acting at the central-type benzodiazepines receptors on blood glucose levels in mice were studied. 2. Clonazepam, injected intraperitoneally in doses of 0.625-5 mg, produced a dose-dependent increase in blood glucose 30 min after administration. 3. The hyperglycaemic effect of clonazepam (2.5 mg/kg, i.p.) was dose-dependently reduced by Ro 15-1788 (10-40 mg/kg, i.v.), a benzodiazepine antagonist. 4. Ro 5-3663, a GABA antagonist which may act at the picrotoxinin site, produced a significant increase in blood glucose (5 or 10 mg/kg, i.p.); however, when given together with clonazepam (2.5 mg/kg, i.p.) attenuation of the hyperglycaemic effect was observed. 5. Pk 8165, a partial agonist, lacked an effect on blood glucose over the dose range of 5-20 mg/kg, i.p. but caused a slight increase in blood glucose in a dose of 40 mg/kg, i.p.

Topics: Animals; Benzodiazepinones; Blood Glucose; Clonazepam; Dose-Response Relationship, Drug; Drug Interactions; Flumazenil; Mice; Mice, Inbred ICR; Quinolines; Receptors, GABA-A

Ro 5-3663 is a convulsant 1,4-benzodiazepine that does not act at the benzodiazepine, but at the picrotoxin, site. To characterize the behavioural actions of Ro 5-3663, a comparison was made between its effects and those of picrotoxin, when combined with several compounds that act at the GABA-benzodiazepine receptor complex. The quinolines, PK 8165, PK 9084 and CGS 8216 caused myoclonic jerks when combined with subconvulsant doses of Ro 5-3663 or picrotoxin; in combination with picrotoxin they also caused full tonic-clonic convulsions. Ro 15-1788 (1, 10 mg kg-1) caused myoclonic jerks when it was given 10 min before, or at the same time as, subconvulsant doses of either compound. Diazepam (2, 4 mg kg-1) was anticonvulsant against both compounds. However, Ro 15-1788 (10, 20 mg kg-1, 20 min before), PK 8165 (80 mg kg-1) and PK 9084 (60 mg kg-1) were effective only against the convulsions induced by Ro 5-3663. It is not possible to determine whether these differences between Ro 5-3663 and picrotoxin are quantitative or qualitative.

Topics: Animals; Benzodiazepinones; Chemical Phenomena; Chemistry; Convulsants; Diazepam; Drug Synergism; Flumazenil; Male; Mice; Picrotoxin; Pyrazoles; Quinolines; Seizures