Brain uptake and receptor binding of two [11C]labelled selective high affinity NK1-antagonists, GR203040 and GR205171--PET studies in rhesus monkey

Neuropharmacology. 2000 Feb 14;39(4):664-70. doi: 10.1016/s0028-3908(99)00182-3.


Two high affinity and selective NK1-receptor antagonists, GR203040 and GR205171, were labelled with 11C and used in a series of experiments in rhesus monkeys. The purpose of these studies was to evaluate the brain uptake pattern and to explore the potential use of these compounds as PET ligands to characterise NK1-receptor binding. Seventeen studies were carried out with [11C]GR205171 and five experiments with [11C]GR203040, including baseline studies and studies performed after a 5 min infusion of cold compound at doses between 0.05 and 1 mg/kg. Both compounds demonstrated a significant and rapid uptake in the brain, but the uptake of [11C]GR205171 was more than double the uptake of [11C]GR203040. At tracer doses of [11C]GR205171 and all doses of [11C]GR203040 the uptake reached a plateau with no washout during the examination time, whereas [11C]GR205171 after pre-treatment with cold GR205171 showed a significant washout. Using a model with the cerebellum as reference, a method for quantitation was applied to the studies with [11C]GR205171 and the results indicated that the highest specific binding was in the striatum. The pre-treatment dose of cold GR205171 needed for 50% inhibition of binding was less than 0.04 mg/kg. The studies indicated that [11C]GR205171 could be used for the in vivo characterisation of NK1-receptor binding.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Ligands
  • Macaca mulatta
  • Neurokinin-1 Receptor Antagonists
  • Piperidines / metabolism*
  • Piperidines / pharmacokinetics
  • Protein Binding
  • Receptors, Neurokinin-1 / metabolism*
  • Tetrazoles / metabolism*
  • Tetrazoles / pharmacokinetics
  • Tomography, Emission-Computed


  • Carbon Radioisotopes
  • Ligands
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Receptors, Neurokinin-1
  • Tetrazoles
  • (2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine
  • vofopitant