A NOVEL BENZODIAZEPINE INVERSE AGONIST, S-8510, AS A COGNITIVE ENHANCER

1. Pharmacological actions of a novel benzodiazepine receptor ligand, S-8510 ,7,9-tetrahydroimidazo[4,5-d]pyrano[4,3-b]pyridine monophosphat e monohydrate), were examined in in vitro and in vivo studies. 2. S-85 10 was characterized as a partial inverse agonist with a modest GABA r atio and low efficacy. 3. S-8510 ameliorated memory impairment induced by cholinergic deficit in the water maze paradigm of Wistar rats. 4. S-8510 augmented LTP of the Schaffer collateral/commissural fiber-CA1 synapses in the hippocampal slice preparations of SD rat. 5. S-8510 in creased the extracellular levels of acetylcholine and noradrenaline in the hippocampus of Wistar rat. 6. S-8510 selectively potentiated pent ylenetetrazol-induced convulsion without affecting minimal electroconv ulsive shock- or strychnine-induced convulsion in ddY mice. 7. S-8510 failed to induce any sign of anxiety in the Wistar rat pro-conflict te st. 8. S-8510 showed antidepressant-like pharmacological actions in dd Y mice. 9. These results suggest that S-8510 can be used as a therapeu tic drug for senile dementia, including Alzheimer's disease with littl e risk for inducing anxiety or convulsion.