S-(+)-aporphines are not selective for human D3 dopamine receptors.
1. Our aim was to test the hypothesis that selectivity for D3 dopamine (DA) receptors may contribute to limbic anti-DA selectivity of S-(+)-aporphine DA partial agonists. 2. Affinity was tested with 3H-emonapride, using human D3 receptors in mouse fibroblasts and D2 receptors in rat striatal tissue. 3. D3 receptors showed a picomolar affinity for 3H-emonapride, Na+ dependence, and reversible saturability, as well as stereoselectivity. Confirmatory or novel D3/D2 pharmacologic selectivity was found with several benzamides, thioxanthenes, buspirone, GBR-12909, and DA agonists including hydroxyaminotetralins [ADTN, (+)-7-OH-DPAT, (-)-PPHT and its fluorescein derivative], (-)-N-propylnorapomorphine, (-)-3-PPP, (-)-quinpirole, and SDZ-205-502, but neither aminoergoline nor (+)-aporphine partial agonists. 4. The results extend pharmacologic characterization of D3-transfected cell membranes but fail to account for the high limbic anti-DA selectivity of S-(+)-aporphines.
Mailman Research Center, McLean Division-Massachusetts General Hospital, Belmont 02178.
N S
NS
Kula
R J
RJ
Baldessarini
J W
JW
Kebabian
J L
JL
Neumeyer
D000818:Animals; D001060:Aporphines / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3
D001060:Aporphines; C493593:DRD3 protein, human; C493594:Drd3 protein, mouse; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3