In vitro effects of hydroxybenzaldehydes from Gastrodia elata and their analogues on GABAergic neurotransmission, and a structure-activity correlation

The present study was designed to characterize the modulatory effects of the constituents of Gastrodia elata and their analogues on the GABAergic neurotransmission. 4-Hydroxybenzaldehyde (1) and 4-hydroxy-3-methoxybenzaldehyde (4) inhibited potently the activity of GABA transaminase (IC50 = 4.1 and 5.4 mug/ml, respectively), while the activity of another constituent, 4-hydroxybenzyl alcohol (2), was very weak. Further investigation with 10 analogues revealed a structure-activity correlation, suggesting that the aldehyde group and the hydroxy group at C-4 are necessary for the inhibitory effect on the enzyme activity. Some potent enzyme inhibitors were examined for the effect on the radioligands to the GABAA receptor complexes of rat cerebral cortices. Among them, the component 4 dose-dependently increased (20-30%) the binding of [H-3]flunitrazepam in the presence of GABA.