Autoradiographic evaluation of [3H]CUMI-101, a novel, selective 5-HT1AR ligand in human and baboon brain

Brain Res. 2013 Apr 24:1507:11-8. doi: 10.1016/j.brainres.2013.02.035. Epub 2013 Feb 27.

Abstract

[11C]CUMI-101 is the first selective serotonin receptor (5-HT1AR) partial agonist radiotracer for positron emission tomography (PET) tested in vivo in nonhuman primates and humans. We evaluated specific binding of [3H]CUMI-101 by quantitative autoradiography studies in postmortem baboon and human brain sections using the 5-HT1AR antagonist WAY-100635 as a displacer. The regional and laminar distributions of [3H]CUMI-101 binding in baboon and human brain sections matched the known distribution of [3H]8-OH-DPAT and [3H]WAY-100635. Prazosin did not measurably displace [3H]CUMI-101 binding in baboon or human brain sections, thereby ruling out [3H]CUMI-101 binding to α1-adrenergic receptors. This study demonstrates that [11C]CUMI-101 is a selective 5-HT1AR ligand for in vivo and in vitro studies in baboon and human brain.

MeSH terms

  • Animals
  • Autoradiography
  • Brain / anatomy & histology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Drug Partial Agonism
  • Humans
  • Ligands
  • Papio
  • Piperazines / metabolism*
  • Positron-Emission Tomography
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin 5-HT1 Receptor Agonists / metabolism*
  • Triazines / metabolism*
  • Tritium

Substances

  • (O-methyl-11C) 2-(4-(4-(3-methoxyphenyl)piperazin-1-yl)-butyl)-4-methyl-2H-(1,2,4)-triazine-3,5-dione
  • Ligands
  • Piperazines
  • Serotonin 5-HT1 Receptor Agonists
  • Triazines
  • Tritium
  • Receptor, Serotonin, 5-HT1A