gamma-Aminobutyric acid (GABA) receptor stimulation. II. Specificity of progabide (SL 76002) and SL 75102 for the GABA receptor

Progabide and its immediate metabolite SL 75102 displace [3H]gamma-aminobutyric acid (GABA), [3H]muscimol and [3H]isoguvacine from their binding sites to membranes prepared from rat brain or human cerebellum and increase (SL 75102) [3H]flunitrazepam binding to rat cerebral cortex membranes. In contrast, these compounds have very weak or no effects on alpha or beta noradrenergic, histamine, muscarinic cholinergic or glycine receptors or on the [3H]imipramine or [3H]kainate binding sites. Neither progabide nor SL 75102 inhibit GABA synthesis, metabolism or uptake. Also, the uptake of norepinephrine, serotonin and dopamine into synaptosomes of cerebral regions is not affected by progabide. [3H]GABA release from substantia nigra slices is decreased by SL 75102 and progabide, in agreement with the hypothesis of a GABAergic autoreceptor controlling GABA release from its nerve terminals. These data suggest a specific agonist action of progabide and SL 75102 on GABA receptors.