Synthesis, radiolabeling and evaluation of novel amine guanidine derivatives as potential positron emission tomography tracers for the ion channel of the N-methyl-D-aspartate receptor

Pieter J. Klein, Marion Chomet, Athanasios Metaxas, Johannes A. M. Christiaans, Esther Kooijman, Robert C. Schuit, Adriaan A. Lammertsma, Bart N. M. van Berckel, Albert D. Windhorst

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The N-Methyl-d-Aspartate receptor (NMDAR) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. The aim of this study was to develop a positron emission tomography (PET) ligand to assess the bio-availability of the NMDAR ion channel in vivo. A series of tri-N-substituted diarylguanidines was synthesized and their in vitro binding affinities for the NMDAR ion channel assessed in rat forebrain membrane fractions. Compounds 21, 23 and 26 were radiolabeled with either carbon-11 or fluorine-18 and ex vivo biodistribution and metabolite studies were performed in Wistar rats. Biodistribution studies showed high uptake especially in prefrontal cortex and lowest uptake in cerebellum. Pre-treatment with MK-801, however, did not decrease uptake of the radiolabeled ligands. In addition, all three ligands showed fast metabolism.
Original languageEnglish
Pages (from-to)143-160
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 8 Aug 2016


  • NMDA
  • Non-competitive antagonists
  • PET
  • Radiolabeling
  • SAR

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