title: RBI-257: a highly potent dopamine D4 receptor-selective ligand.
abstract: 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.
authors.affiliation: Consolidated Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Kula
authors.forename: R J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: J W
authors.initials: JW
authors.lastname: Kebabian
authors.forename: V
authors.initials: V
authors.lastname: Bakthavachalam
authors.forename: L
authors.initials: L
authors.lastname: Xu
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D006224:Cricetinae; D015259:Dopamine Agents / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007536:Isomerism; D008024:Ligands; D008566:Membranes / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050638:Receptors, Dopamine D4
chemical_list: D000631:Aminopyridines; C493599:DRD4 protein, human; D015259:Dopamine Agents; C493601:Drd4 protein, rat; D008024:Ligands; D010880:Piperidines; C108520:RBI 257; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; C106117:U 101958