Identification of potential GABA-mimetics by their actions on brain GABA recognition sites

In an attempt to identify potential anticonvulsant compounds, 18 structural analogues of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) were tested for their ability to inhibit GABA receptor binding, sodium-dependent GABA binding and GABA aminotransferase activity in synaptic membranes from mouse brain. Nine inhibitors of receptor binding were found. The most potent was N-(thiocarbamoyl)glycine (Ki = 18 microM). However, this compound had no real effect on Na+ -dependent GABA binding nor on the activity of GABA aminotransferase. In addition, it was unable to enhance the binding of [3H]flunitrazepam as GABA agonists usually do. This could indicate that this inhibitor is, rather, a GABA receptor antagonist. Even though no particularly potent inhibitors of any of the GABA recognition sites were found, this technique nevertheless demonstrates how simple in vitro assays can be used to find drugs exhibiting potential GABA-mimetic activity.