YM-50001: A novel, potent and selective dopamine D4 receptor antagonist

WE investigated some in vitro pharmacological properties of a novel human dopamine D2-like receptor antagonist, YM-50001 [(R)-5-chloro-4-cyclopropylcarbonylamino-2-methoxy-N-[1-(3-methoxybenzyl)-3-pyrrolidinyl]benzamide monooxalate]. Receptor binding studies revealed that YM-50001 had a potent affinity for human D4 receptors (Ki = 5.62 nM). YM-50001 displayed weak or negligible affinity for other neurotransmitter receptors including human D2 and D3 receptors. YM-50001 shifted the dopamine response curve on each human D2-like receptor subtype-mediated low-Km GTPase activity to the right. YM-50001 also exhibited good D4 selectivity with respect to D2-like receptor antagonism in the functional assay. These results indicate that YM-50001 is a novel, potent and selective D4 receptor antagonist.