The naphtosultam derivative RP 62203 (fananserin) has high affinity for the dopamine D-4 receptor

The dopamine D-4 receptor is a potential target for novel antipsychotic drugs. Most available compounds with affinity for the dopamine D-4 receptor also bind to dopamine D-2 receptors. This report describes the affinity of the 5-HT2A receptor antagonist RP 62203 (fananserin) for the human dopamine D-4 receptor. Fananserin displaces [H-3]spiperone binding to recombinant human dopamine D-4 receptors with a K-i of 2.93 nM. This compares with an affinity (K-i) of 0.37 nM for the rat 5-HT2A receptor and of 726 nM for the rat dopamine D-2 receptor. [H-3]Fananserin can be used to label the recombinant dopamine D-4 receptor expressed in Chinese hamster ovary cells with a K-D of 0.725 nM. Fananserin is, thus, the first compound to be reported that distinguishes between dopamine D-4 and D-2 receptors.