THE EFFECTS OF RU-33965 AND RU-34030, 2 NEW 3-CYCLOPROPYL CARBONYL IMIDAZOBENZODIAZEPINES, ON GABA(A) 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 GABA(A) synaptic tran smission in rat cerebellar slices. The action of the full benzodiazepi ne agonist RU 32007 and the inverse agonist Ro19-4603 were tested for comparison. 2. Extracellular recordings were made from the Purkinje ce ll layer of the cerebellar slices and inhibition induced by just thres hold electrical stimulation of the parallel fibres was bicuculline sen sitive. 3. The major effect of RU 32007 when examined at 100 nM and 1 mu M was to increase the GABA(A) mediated inhibition in the slice. 4. In contrast the major effect of the inverse agonist Ro19-4603 was to r educe the period of inhibition. 5. RU 33965 and RU 34030 at 10 and 1 m u M respectively either had little effect on GABA(A) mediated inhibiti on or decreased it slightly. 6. RU 34030, 1 mu M, abolished the agonis t effect of RU 32007, 1 mu M. 7. The effects of RU 32007 and Ro19-4603 were abolished by the benzodiazepine anatagonist flumazenil. 8. It is concluded that bath RU 33965 and RU 34030 have marginal inverse agoni st properties.