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.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism; D004974:Etazolate / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology*; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D003975:Diazepam; D004974:Etazolate; D009539:Nicotinic Acids; D010852:Picrotoxin; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; C031012:dihydropicrotoxinin receptor; C017230:dihydropicrotoxinin