[¹²⁵I]Thienylphencyclidine, a novel ligand for the NMDA receptor

We have monitored the binding of [¹²⁵I]thienylphencyclidine ([¹²⁵I]TCP), a novel high affinity radioiodinated ligand that specifically recognizes the NMDA (N-methyl-D-aspartate) receptor in rat brain membranes. [¹²⁵I]TCP binds with an affinity of about 30 nM, and recognizes a similar number of binding sites to previously employed ligands for this receptor. [¹²⁵I]TCP binding is characterized by slow association and dissociation rates, and the latter can be modified by the addition of Mg²⁺ or Zn²⁺, as previously described for [³H]dizocilpine ([³MK801). Other phencylidine-like ligands displaced [¹²⁵I]TCP binding with the order of potency dizocilpine > thienylphencyclidine > ITCP > phencyclidine > ketamine. The binding of [¹²⁵I]TCP was also increased by NMDA and glycine-site agonists and inhibited by antagonists of these sites. Surprisingly, however, the polyamines spermidine and spermine did not increase [¹²⁵I]TCP, even though the polyamine antagonist arcaine was an effective inhibitor of binding. These results show that [¹²⁵I]TCP is a useful ligand for the NMDA receptor complex that binds to the receptor in a manner that is qualitatively distinct from previously described ligands.