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

Eur J Pharmacol. 1997 Jul 23;331(2-3):333-6. doi: 10.1016/s0014-2999(97)01065-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminopyridines / pharmacology*
  • Animals
  • Brain Chemistry / drug effects
  • Cricetinae
  • Dopamine Agents / pharmacology
  • Guinea Pigs
  • Humans
  • In Vitro Techniques
  • Isomerism
  • Ligands
  • Membranes / metabolism
  • Piperidines / pharmacology*
  • Radioligand Assay
  • Rats
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D4


  • Aminopyridines
  • DRD4 protein, human
  • Dopamine Agents
  • Drd4 protein, rat
  • Ligands
  • Piperidines
  • RBI 257
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4
  • U 101958