Isomeric selectivity at dopamine D3 receptors.
Racemic 7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) shows greater affinity for limbic-selective dopamine D3 receptors than for more ubiquitous dopamine D2 receptors. R(+)-7-OH-DPAT was prepared and evaluated in radioreceptor assays using membranes of fibroblasts expressing the human dopamine D3 receptor as well as rat striatal membranes containing dopamine D2 receptors. This enantiomer had 2-fold greater D3 affinity than the racemate and similarly greater D3 vs. D2 selectivity (64-fold). The results may facilitate development of D3 selective agents and evaluation of functions of these receptors.
Baldessarini
R J
RJ
Mailman Research Center, McLean Division of Massachusetts General Hospital.
Kula
N S
NS
McGrath
C R
CR
Bakthavachalam
V
V
Kebabian
J W
JW
Neumeyer
J L
JL
D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D011869:Radioligand Assay; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000378:metabolism; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000378:metabolism*; D014162:Transfection
C493593:DRD3 protein, human; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; C045989:eticlopride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin