Skip to main content
NCBI home page
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 1994 Apr;14(2):185–191. doi: 10.1007/BF02090784

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

Nora S Kula 1, Ross J Baldessarini 1,2,✉, John W Kebabian 3, John L Neumeyer 3
PMCID: PMC11566802  PMID: 7842476

Abstract

1. Our aim was to test the hypothesis that selectivity for D3 dopamine (DA) receptors may contribute to limbic anti-DA selectivity ofS-(+)-aporphine DA partial agonists.

2. Affinity was tested with3H-emonapride, using human D3 receptors in mouse fibroblasts and D2 receptors in rat striatal tissue.

3. D3 receptors showed a picomolar affinity for3H-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 ofS-(+)-aporphines.

Key words: aminoergolines, aminotetralins, aporphines, dopamine, D2, D3, receptors, striatum, transfection

References

  1. Baldessarini, R. J., Kula, N. S., Campbell, A., Bakthavachalam, V., Yuan, J., and Neumeyer, J. L. (1992). Prolonged D2 antidopaminergic activity of alkylating and nonalkylating derivatives of spiperone in rat brain.Mol. Pharmacol.42856–863. [PubMed] [Google Scholar]
  2. Baldessarini, R. J., Kula, N. S., McGrath, C., Kebabian, J. W., and Neumeyer, J. L. (1993). Isomeric selectivity of D3 dopamine receptors.Eur. J. Pharmacol.239269–270. [DOI] [PubMed] [Google Scholar]
  3. Boundy, V. A., Luedke, R. R., Gallitano, A. L., Smith, J. E., Filtz, T. M., Kallen, R. G., and Molinoff, P. B. (1993). Expression and characterization of the rat D3 dopamine receptor: Pharmacologic properties and development of antibodies.J. Pharmacol. Exp. Ther.2641002–1011. [PubMed] [Google Scholar]
  4. Bouthenet, M. L., Souil, E., Martres, M. P., Sokoloff, P., Giros, B., and Schwartz, J. C. (1991). Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization biochemistry: Comparison with dopamine D2 receptor mRNA.Brain Res.564203–219. [DOI] [PubMed] [Google Scholar]
  5. Campbell, A., Yeghiayan, S., Baldessarini, R. J., and Neumeyer, J. L. (1991). Selective antidopaminergic effects of S(+)-N-n-propylnoraporphines in limbic vs. extrapyramidal sites in rat brain: Comparisons with typical and atypical antipsychotic agents.Psychopharmacology103323–329. [DOI] [PubMed] [Google Scholar]
  6. Campbell, A., Baldessarini, R. J., and Yeghiayan, S. (1992). Antagonism of limbic and extrapyramidal actions of intracerebrally injected dopamine by ergolines with partial D2 agonist activity in the rat.Brain Res.592348–352. [DOI] [PubMed] [Google Scholar]
  7. Campbell, A., Baldessarini, R. J., and Neumeyer, J. L. (1993). Altered spontaneous behavior and sensitivity to apomorphine in rats following pretreatment with S(+)-aporphines or fluphenazine.Psychopharmacology111351–358. [DOI] [PubMed] [Google Scholar]
  8. Figur, L. M., Evans, D. L., Stratman, N. C., and Lahti, R. A. (1992). The dopamine D4 and D2 receptors: Comparison of neuroleptic binding activities.Soc. Neurosci. Abstr.18375. [Google Scholar]
  9. Foulon, C., Kung, M. P., and Kung, H. F. (1993). Synthesis of (R,S)-2′-trans-7-hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)amino]tetralin (Trans-7-OH-PIPAT): A new D3 dopamine receptor ligand.J. Med. Chem.361499–1500. [DOI] [PubMed] [Google Scholar]
  10. Kebabian, J. W., and Calne, D. B. (1979). Multiple receptors for dopamine.Nature22793–96. [DOI] [PubMed] [Google Scholar]
  11. Landwehrmeyer, B., Mengod, G., and Palacios, J. M. (1993). Differential visualization of dopamine D2 and D3 receptor sites in rat brain: a comparative study using in situ hybridization histochemistry and ligand binding autoradiography.Eur. J. Neurosci.5145–153. [DOI] [PubMed] [Google Scholar]
  12. Lévesque, D., Diaz, J. Pilon, C., Martres, M. P., Giros, B., Souil, E., Schott, D., Morgat, J. L., and Schwartz, J. C. (1992). Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin.Proc. Natl. Acad. Sci. USA898155–8159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Leysen, J. E., Janssen, P. M., Schotte, A., Luyten, W. H., and Megens, A. A. (1993). Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: Role of 5HT2 receptors.Psychopharmacology112S40-S54. [DOI] [PubMed] [Google Scholar]
  14. Malmberg, Å., Jackson, D. M., Erikssonm, A., and Mohell, N. (1993). Unique binding characteristics of antipsychotic agents interacting with human dopamine D2A, D2B, and D3 receptors.J. Pharmacol. Exp. Ther.43749–754. [PubMed] [Google Scholar]
  15. Seabrook, G. R., Patel, S., Marwood, R., Emms, F., Knowles, M. R., Freedman, S. B., and McAllister, G. (1992). Stable expression of human D3 dopamine receptors in GH4C1 pituitary cells.Fed. Eur. Biochem. Soc. Lett.312123–126. [DOI] [PubMed] [Google Scholar]
  16. Seeman, P., and Van Tol, H. H. (1993). Dopamine D4 receptors bind inactive (+)-aporphines suggesting neuroleptic role: Sulpiride not stereoselective.Eur. J. Pharmacol.233173–174. [DOI] [PubMed] [Google Scholar]
  17. Sibley, D. R., Monsma, F., Jr., and Shen, Y. (1993). Molecular neurobiology of dopaminergic receptors.Int. Rev. Neurobiol.35391–415. [DOI] [PubMed] [Google Scholar]
  18. Sokoloff, P., Giros, B., Martres, M. P., Bouthenet, M. L., and Schwartz, J. C. (1990). Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics.Nature347146–151. [DOI] [PubMed] [Google Scholar]
  19. Sokoloff, P., Andrieux, M., Besançon, R., Pilon, C., Martres, M. P., Giros, B., and Schwartz, J. C. (1992). Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: Comparison with D2 receptor.Eur. J. Pharmacol.225331–337. [DOI] [PubMed] [Google Scholar]
  20. Tang, L., Todd, R. D., Heller, A., and O'Malley, K. (1994). Pharmacological and functional characterization of D2, D3, and D4 dopamine receptors in fibroblast dopaminergic cell lines.J. Pharmacol. Exp. Ther.268495–502. [PubMed] [Google Scholar]
  21. Todd, R. D., and O'Malley, K. L. (1993). Family ties: Dopamine D2-like receptor genes.RBI Neurotransmiss.91–4. [Google Scholar]
  22. Watts, V. J., Lawler, C. P., Knoerzer, T., Mayleben, M. A., Neve, K. A., Nichols, D. E., and Mailman, R. B. (1993). Hexahydrobenzo[a]phenanthridines: Novel dopamine D3 receptor ligands.Eur. J. Pharmacol.239271–273. [DOI] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES