Two types of cage convulsant action at the GABA-gated chloride channel

Cage convulsants appear to fall into two groups based on correlations between their potency for inhibiting [35S]t-butylbicyclophosphorothionate binding or gamma-aminobutyric acid-stimulated 36chloride uptake in brain membrane preparations and their toxicity to mice. Polychlorocycloalkanes, picrotoxinin and 2,6,7-trioxabicyclo[2.2.2]octanes with large 1-substituents exhibit high potency in these in vitro brain membrane systems relative to their toxicity (type A action). In contrast, trioxabicyclooctanes with small 1-substituents and tetramethylenedisulfotetramine show much lower in vitro potency relative to their toxicity (type B action). Compounds with type A action are generally more potent insecticides than those with type b action.