Molecular interactions of etazolate with benzodiazepine and picrotoxinin binding sites

Pyrazolopyridines, such as etazolate (SQ 20009), enhance [3H]diazepam binding to a Lubrol-solubilized fraction that has specific binding sites for 3H benzodiazepines, [alpha-3H]dihydropicrotoxinin (DHP) and [3H]muscimol. Etazolate enhancement of [3H]diazepam binding was inhibited by picrotoxinin. Furthermore, etazolate inhibited the [3H]DHP binding in a Lubrol-solubilized fraction with an IC50 value of 6-8 microM. These results provide evidence that etazolate, like pentobarbital, modulates benzodiazepine binding via the DHP-sensitive site of the benzodiazepine-GABA receptor-ionophore complex.