gamma-Aminobutyric acid receptor binding antagonism by the amidine steroid RU5135.
The novel convulsant amidine steroid RU5135 inhibited gamma-aminobutyric acid receptor binding in membranes from seven regions of rat brain (IC50 = 11 +/- 2 nM against [3H]muscimol and 0.8 +/- 0.2 nM against [3H]bicuculline methochloride), apparently lowering the number of binding sites labeled with gamma-aminobutyric acid receptor agonists or antagonists. The steroid reversed the enhancement of benzodiazepine receptor binding by gamma-aminobutyric acid, pentobarbital, and etazolate, but did not inhibit the binding of the convulsant [35S]t-butyl bicylophosphorothionate. Thus, RU5135 shows very potent in vitro actions more resembling those of the gamma-aminobutyric acid site antagonist, bicuculline, than the chloride channel antagonist, picrotoxin.
D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D001463:Barbiturates / Q000378:metabolism; D001569:Benzodiazepines / Q000378:metabolism; D001640:Bicuculline / Q000378:metabolism; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000731:Androstanes; D001378:Azasteroids; D001463:Barbiturates; D011963:Receptors, GABA-A; D013260:Steroids, Heterocyclic; D001569:Benzodiazepines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; C032061:RU 5135; D001640:Bicuculline