In vivo labeling of central benzodiazepine receptors with the partial inverse agonist [3H]Ro 15-4513

B. Sadzot, J. J. Frost, H. N. Wagner

Research output: Contribution to journalArticle

Abstract

Ro 15-4513 is an imidazobenzodiazepine and a partial inverse agonist at the central benzodiazepine recetors (BZDr). It has been shown to antagonize behavioral and biochemical effects of ethanol. In vivo binding of [3H]Ro 15-4513 was evaluated in mouse brain. After intravenous injection, [3H]Ro 15-4513 was readily taken up by the brain and distributed to brain areas enriched in benzodiazepine receptors. Binding was specific for central BZDr, saturable and reversible. A high degree of specific binding, relative to non-specific binding, was achieved. Analysis of dissociation kinetics revealed that [3H]Ro 15-4513 was retained significantly longer in hippocampus compared to other brain regions. In view of the known distribution of benzodiazepine receptor subtypes, this suggests that, in vivo, [3H]Ro 15-4513 has a higher affinity for benzodiazepine receptors type II and may explain quantitative differences in the regional distribution of this ligand compared to the antagonist [3H]Ro 15-1788. We conclude from these studies that Ro 15-4513 is a suitable ligand for in vivo studies of benzodiazepine receptors. Labeled with a positron-emitting isotope, it could be used with positron emission tomography to study BZDr in man under a variety of conditions.

Original languageEnglish (US)
Pages (from-to)128-135
Number of pages8
JournalBrain Research
Volume491
Issue number1
DOIs
StatePublished - Jul 3 1989

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Keywords

  • Benzodiazepine receptor
  • In vivo binding
  • Ro 15-1788
  • Ro 15-4513

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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