Multiple fluorescent ligands for dopamine receptors. I. Pharmacological characterization and receptor selectivity

Anne C. Barton, Hee Chol Kang, Mario S. Rinaudo, Frederick J. Monsma, Rose M. Stewart-Fram, James A. Macinko, Richard P. Haugland, Marjorie A. Ariano, David R. Sibley

Research output: Contribution to journalArticlepeer-review


We report the synthesis and pharmacological characterization of novel fluorescently labeled ligands with high affinity and specificity for D1 and D2 dopamine receptors. D1-selective antagonist probes have been synthesized using (R,S)-5-(4′-aminophenyl)-8-chloro-2,3,4,5-tetrahydro-3-methyl-[1H]-3-benzazepin-7-ol, the 4′-amino derivative of the high affinity D1-selective antagonist, SCH-23390, while D2-selective antagonist probes were synthesized using the high affinity, D2-selective agonist, N-(p-aminophenethyl)spiperone (NAPS). In addition, we have synthesized fluorescent probes using an amino-derivative of the high affinity, D2-selective agonist, 2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT or N-0434). These ligands were coupled to the fluorescent moieties, fluorescein, rhodamine, coumarin, Texas red, Cascade blue, or Bodipy. This resulted in a wide variety of dopaminergic ligands which fluoresce at different wavelengths: Cascade blue and coumarin are blue fluorophores, fluorescein and Bodipy, are yellow-green, and Texas red and rhodamine are red. The interaction of these fluorescent ligands with dopamine and serotonin receptors was evaluated by examining their ability to compete for radioligand binding to D1 and D2 dopamine receptors and 5-HT1A, 5-HT1C and 5-HT2 serotonin receptors. We report here that these novel fluorescent ligands exhibit high affinity and, in general, selectivity for either D1 or D2 dopamine receptors. In addition, we demonstrate that the fluorescent derivatives of PPHT retain the full agonist efficacy exhibited by the parent compound. The availability of fluorescent ligands for D1 and D2 dopamine receptors should enable the visualization of these receptors at the cellular and subcellular levels in the CNS as well as in following the dynamics of agonist-receptor interactions in cultured cells.

Original languageEnglish (US)
Pages (from-to)199-207
Number of pages9
JournalBrain Research
Issue number2
StatePublished - May 3 1991


  • D-receptor
  • D-receptor
  • Dopamine receptor
  • Fluorescent ligand
  • Serotonin receptor

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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