Interactions of some anaesthetic,convulsant, and anticonvulsant drugs at GABA-benzodiazepine receptor-ionophore complexes in rat brain synaptosomal membranes

The effects of several anaesthetic, convulsant and anticonvulsant drugs were studied upon high affinity 3H]GABA and 3H]diazepam binding to rat brain synaptosomal membranes in chloride-containing incubation buffers at 25 degrees C, conditions under which pentobarbitone extensively enhanced binding of both ligands to GABA-benzodiazepine-receptor-ionophore complexes. Of the compounds studied, only (+)-etomidate enhanced both GABA and diazepam binding; the sedative-hypnotic glutethimide weakly enhanced GABA binding while inhibiting diazepam binding. Several drugs, including beta-butyl-beta-methyl-glutarimide, phenobarbitone, pentylenetetrazole, and ketamine reversed the enhancement of GABA binding by pentobarbitone (500 microM) while not altering basal GABA or diazepam binding. Enhancement of high affinity GABA binding does not appear to be a general property of sedative or anticonvulsant drugs.