[³H]S33084: a novel, selective and potent radioligand at cloned, human dopamine D₃ receptors

Abstract.

The novel, selective dopamine D₃ receptor antagonist, S33084 [(3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl)benzamide], was tritium-labelled to 59 Ci/mmol specific activity. Determination of association and dissociation rate constants at recombinant, human (h) D₃ receptors stably expressed in Chinese hamster ovary (CHO) cells yielded a K _d value (0.16 nM) comparable to that observed in saturation binding experiments (0.17 nM). The competition binding profile of [³H]S33084 with diverse D₃ receptor agonists and antagonists correlated highly (0.99) with that of [³H]spiperone. In conclusion, [³H]S33084 is a highly potent and selective radioligand at dopamine D₃ receptors, which should be of considerable use for their characterisation.