CAGE CONVULSANTS INHIBIT PICROTOXININ BINDING

Several types of cage compounds are highly toxic to mammals. These include tetramethylene disulfotetramine, alkyl bicyclophosphate esters (4-alkyl-1-phospha-2, 6,7-trioxabicyclo [2.2.2] octane-1-oxides), ortho carboxylic acids of related structure (1-substituted-4-alkyl-2,6,7-trioxabicyclo [2.2.2] octanes), and silicon-nitrogen (silatrane) analogues (1-substituted-2,8,9-trioxa-5-aza-1-silabicyclo [3.3.3] undecanes). These compounds have convulsant activity resembling the action of picrotoxin, a synaptic antagonist of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA). In this study, numerous examples of these cage compounds have been found to have no effect on GABA receptor binding sites in mammalian brain; rather, they inhibit potently the binding of dihydropicrotoxinin to membrane sites related to the chloride ion channels which are regulated by GABA receptors. © 1979.