In vivo labeling of central benzodiazepine receptors with the partial inverse agonist [3H]Ro 15-4513.
Ro 15-4513 is an imidazobenzodiazepine and a partial inverse agonist at the central benzodiazepine receptors (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.
Sadzot
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Department of Radiology, John Hopkins University School of Medicine, Baltimore, MD 21205.
Frost
J J
JJ
Wagner
H N
HN
D000818:Animals; D001386:Azides / Q000378:metabolism*; D001569:Benzodiazepines / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D001386:Azides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C042957:Ro 15-4513