The effects of RU 33965 and RU 34030, two new 3-cyclopropyl carbonyl imidazobenzodiazepines, on GABAA receptor-mediated synaptic transmission in cerebellar slices in the rat.
1. Two 3-cyclopropyl carbonyl imidazobenzodiazepines, RU 33965 and RU 34030, were tested for their ability to modulate GABAA synaptic transmission in rat cerebellar slices. The action of the full benzodiazepine agonist RU 32007 and the inverse agonist Ro19-4603 were tested for comparison. 2. Extracellular recordings were made from the Purkinje cell layer of the cerebellar slices and inhibition induced by just threshold electrical stimulation of the parallel fibres was bicuculline sensitive. 3. The major effect of RU 32007 when examined at 100 nM and 1 microM was to increase the GABAA mediated inhibition in the slice. 4. In contrast the major effect of the inverse agonist Ro19-4603 was to reduce the period of inhibition. 5. RU 33965 and RU 34030 at 10 and 1 microM respectively either had little effect on GABAA mediated inhibition or decreased it slightly. 6. RU 34030, 1 microM, abolished the agonist effect of RU 32007, 1 microM. 7. The effects of RU 32007 and Ro19-4603 were abolished by the benzodiazepine antagonist flumazenil. 8. It is concluded that both RU 33965 and RU 34030 have marginal inverse agonist properties.
Ward
R A
RA
Department of Physiology and Pharmacology, University of Southampton, England.
Gardner
C R
CR
Pringle
A
A
Bagust
J
J
Walker
R J
RJ
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011689:Purkinje Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects*
D001570:Benzodiazepinones; D007093:Imidazoles; D011963:Receptors, GABA-A; C078222:RU 33965; C089857:RU 34030