Synthesis and biological evaluation of [11C]talopram and [11C]talsupram: candidate PET ligands for the norepinephrine transporter.

Academic Article

Abstract

  • PET and SPECT ligands for the norepinephrine transporter (NET) will be important tools for studying the physiology, pathophysiology and pharmacology of the CNS noradrenergic system in vivo. A series of candidate NET ligands were synthesized and characterized in terms of their affinity for human monoamine transporters. The two most promising compounds, talopram and talsupram, were radiolabeled with carbon-11 and evaluated through biodistribution studies in rats and PET imaging studies in a rhesus monkey. Although both compounds displayed high affinity and selectivity for the human NET in vitro, these compounds did not enter the CNS in adequate amounts to be used in PET imaging studies.
  • Published In

    Keywords

  • Alkylation, Animals, Benzofurans, Binding, Competitive, Chromatography, High Pressure Liquid, Dopamine Plasma Membrane Transport Proteins, Indicators and Reagents, Ligands, Macaca mulatta, Male, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins, Norepinephrine Plasma Membrane Transport Proteins, Positron-Emission Tomography, Propylamines, Radiopharmaceuticals, Serotonin Plasma Membrane Transport Proteins, Spectrophotometry, Ultraviolet, Stereoisomerism, Symporters, Thiophenes, Tissue Distribution
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23284076
  • Author List

  • McConathy J; Owens MJ; Kilts CD; Malveaux EJ; Camp VM; Votaw JR; Nemeroff CB; Goodman MM
  • Start Page

  • 705
  • End Page

  • 718
  • Volume

  • 31
  • Issue

  • 6