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.

The GABA/benzodiazepine receptor complex in the nervous system of a hypertensive strain of rat.

gamma-Aminobutyric acid (GABA) has been implicated in the development of hypertension and in the regulation of blood pressure. The spontaneously hypertensive rat (SHR) offers an opportunity to explore the role of central GABA and other neurotransmitters in the genesis of high blood pressure. The receptor binding of [3H]GABA, [3H]flunitrazepam, and [3H]glutamate to synaptic membranes from the cerebral cortex and cerebellum of SHR rats were measured in animals of various ages. No significant differences between the SHR and a normotensive control strain of rats were found for any of the assays. The results indicate that in this model of hypertension, neither GABA nor glutamate function are involved, at least not in the cerebral cortex or cerebellum.