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 antipsychoti c drugs. Most available compounds with affinity for the dopamine D-4 r eceptor 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 b inding 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]Fanans erin can be used to label the recombinant dopamine D-4 receptor expres sed 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.