Hexahydrobenzo[a]phenanthridines: novel dopamine D3 receptor ligands

We report that certain substituted hexahydrobenzo[a]phenanthridines are novel high affinity ligands selective for the dopamine D3 receptor. These data demonstrate that substitutions on the heterocyclic nitrogen and the pendant phenyl ring of this nucleus cause a marked increase in both affinity and selectivity for dopamine D3 vs. D2 receptors. Thus, these compounds represent important new tools to study the pharmacology of dopamine D3 receptors, and may also provide an opportunity for the synthesis of new radioligands for dopamine D3 receptors.