BINDING OF THE AMPA RECEPTOR ANTAGONIST [H-3] GYKI-53405 TO XENOPUS BRAIN MEMBRANES

GYKI 52466 AND related 2,3-benzodiazepines are highly selective antagonists of AMPA-evoked responses in rat CNS. However, these compounds do not compete with [H-3]AMPA binding and their site of action remains unclear. Here we show that [H-3]GYKI 53405 binds specifically to Xenopus brain membranes with K-D and B-max values of 4.5 mu M and 35 pmol mg(-1) protein respectively. Binding is increased in the presence of Mg2+ and is unaffected by AMPA or kainate. This is the first report of the binding of a GYKI 52466-related radioligand to any tissue and these results provide an initial step towards the characterization of novel recognition sites which are of considerable therapeutic potential.