Although the rodenticide tetramethylenedisulfotetramine (TETS) was banned worldwide nearly 30 years ago after thousands of accidental or intentional human poisonings, it is still used in some countries.  The high toxicity and ease of preparation of TETS result in it being listed as a potential chemical threat. TETS binds with high affinity as a non-competitive antagonist to the neuronal gamma-aminobutyric acid (GABA) type A receptor (GABAAR). The exact molecular action at the binding site has not been established because an appropriate radioligand was not available. We synthesized [14C]TETS and used accelerator mass spectrometry (AMS)  in neuroreceptor binding studies with rat brain membranes in comparison with the standard GABAAR radioligand 4'-ethynyl-4-n-[3H]propylbicycloorthobenzoate ([3H]EBOB).  This is the first application of AMS to native protein binding assays and illustrates a new in vitro approach for examining binding sites of high affinity ?14C-radioligands. This work was performed in part under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Determining the receptor target of tetramethylenedisulfotetramine

248th National Meeting (2014)

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