RBI-257 - A HIGHLY POTENT DOPAMINE D-4 RECEPTOR-SELECTIVE LIGAND

RBI-257 sopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine), the p-iodob enzyl analog of U-101,958 (1- -isopropoxy-2-pyridinyl)-N-methyl]-amino piperidine had a lower dissociation constant (K-i = 0.3 vs. 2.7 nM) an d higher selectivity than U-101,958 at dopamine D-4 receptors, over do pamine D-2 and D-3 receptors in transfected cell membranes and D-2-lik e sites in rat forebrain. Dopamine D-4 receptor affinity of iodo-isome rs of RBI-257 ranked: para > meta > ortho. RBI-257 had much lower affi nity at D-1 and D-5 dopamine receptors in transfected cells, as well a s dopamine D-1-like receptors, alpha(1), alpha(2) or beta(1,2) adrenoc eptors, sigma(1,2) receptors and 5-HT1A or 5-HT2A receptors, and trans porters for dopamine, norepinephrine or serotonin in rat forebrain tis sue. RBI-257 may be a useful probe or radioligand for brain dopamine D -4 receptors. (C) 1997 Elsevier Science B.V.