RBI-257: a highly potent dopamine D4 receptor-selective ligand.

RBI-257 (1-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperid ine), the p-iodobenzyl analog of U-101,958 (1-benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine) had a lower dissociation constant (Ki = 0.3 vs. 2.7 nM) and higher selectivity than U-101,958 at dopamine D4 receptors, over dopamine D2 and D3 receptors in transfected cell membranes and D2-like sites in rat forebrain. Dopamine D4 receptor affinity of iodo-isomers of RBI-257 ranked: para > meta > ortho. RBI-257 had much lower affinity at D1 and D5 dopamine receptors in transfected cells, as well as dopamine D1-like receptors, alpha1, alpha2 or beta(1,2) adrenoceptors, sigma(1,2) receptors and 5-HT1A or 5-HT2A receptors, and transporters for dopamine, norepinephrine or serotonin in rat forebrain tissue. RBI-257 may be a useful probe or radioligand for brain dopamine D4 receptors.