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 language | English (US) |
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Pages (from-to) | 128-135 |
Number of pages | 8 |
Journal | Brain Research |
Volume | 491 |
Issue number | 1 |
DOIs | |
State | Published - Jul 3 1989 |
Keywords
- Benzodiazepine receptor
- In vivo binding
- Ro 15-1788
- Ro 15-4513
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology
- Clinical Neurology
- General Neuroscience