The chloride channel blocking agent, t-butyl bicyclophosphorothionate, binds to the gamma-aminobutyric acid-benzodiazepine, but not to the glycine receptor in rodents.

The inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA) both activate transmembrane chloride channels of similar physical characteristics. A common ion channel component has therefore been postulated for both the glycine and GABA receptor proteins. Different convulsant drugs as picrotoxin and t-butyl bicyclophosphorothionate (TBPS) have been reported as channel-blocking ligands of the GABA receptor. Here, we show that the distribution of [35S]TBPS binding sites parallels the binding of the GABA receptor ligand [3H]flunitrazepam, but not that of the glycine receptor antagonist [3H]strychnine. Binding was examined in membrane fractions from different regions of the rat CNS and of the mutant mouse spastic, an animal deficient in glycine receptors. Also, affinity purification of the glycine receptor on aminostrychnine-agarose resulted in almost complete removal of [35S]TPBS binding sites from the receptor preparation. It is concluded that TBPS selectively binds to the GABA, but not glycine, receptor chloride channel complex.