||Benzodiazepine receptor (BDZR) ligands were isolated from medicinal herbal extracts of Scutelluria baicalensis Georgi and Hypericum perforatum L. guided by [3H]flunitrazepam displacement assay. Amongst the isolated compounds, 5,7,2'-trihydroxy-6,8-dimethoxyflavone (K36) and 5,7-dihydroxy-6-methoxyflavone (K7) inhibited [3H]fluntrazepam binding to the rat cerebral cortex with Ki of 0.80±0.01nM and 0.89±0.06 μM respectively. These flavonoid derivatives also displayed a GABA shift of 1.20±0.07 and 1.09±0.04 when subjected to [3H]Ro15-1788 binding studies, suggesting that they may behave similarly to that of a partial agonist and an antagonist at the BDZR respectively. 5,7,2'-trihydroxy-6,8-dimethoxyflavone manifested half maximal potentiation of the GABA-evoked current at 24 nM with a Hill coefficient of 0.8 when subjected to electrophysiological studies employing rat recombinant α1β2γ2 GABAA receptors functionally expressed in Xenopus oocytes. K36 itself at 3 μM, however, did not induce any current. The GABA-dependent current was also abolished by the BDZR antagonist Ro15-1788, demonstrating competitive interaction at the BDZR. Oral administration of K36 resulted in significant anxiolysis in the mice elevated plus-maze starting at 4 mg kg-1 twenty minutes after oral administration. Sedative and myorelaxant effects were not detected at the chosen dosage regimen in the holeboard and the horizontal wire tests respectively. Results indicated that K36 exerts its in vivo effects via the BDZR by partial allosteric modulation at the most prevalent mammalian inhibitory neurotransmittor system, the GABAA receptor complex. K7 exhibited some antagonistic properties when orally administered to mice. Behavioral studies confirmed its role as an antagonist only it was also shown that it also manifested receptor subtype selectivity. K7 has no effects as observed in the holeboard, the elevated plus-maze and the horizontal wire tests but was capable of antagonising the anxiolytic and myorelaxant effects induced by diazepam. However. the sedation caused by diazepam was not counteracted even when mice were co-administered 60 mg kg-1 K7. All these clearly suggest that K7 is an antagonist at the BDZR but with selectivity for the receptor subunit mediating the anxiolytic and myorelaxant effects and not that associated with the sedative action of conventional benzodiazepines. Taken together, these results point to the BDZR-mediated effects of the 2 flavonoids with different intrinsic activities. That a partial agonist to an antagonist behavior were observed from the two chosen derivatives also support the notion that flavonoid analogues interacting at the BDZR spanning the whole spectrum of efficacies can be synthesied.