S-(+)-aporphines are not selective for human D3 dopamine receptors

Cell Mol Neurobiol. 1994 Apr;14(2):185-91. doi: 10.1007/BF02090784.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Aporphines / metabolism*
  • Cells, Cultured
  • Humans
  • Male
  • Mice
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2*
  • Receptors, Dopamine D3

Substances

  • Aporphines
  • DRD3 protein, human
  • Drd3 protein, mouse
  • Drd3 protein, rat
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3