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Benzodiazepine Sites (benzodiazepine + site)
Selected Abstracts3,4-Dihydronaphthalen-1(2H)-ones: Novel Ligands for the Benzodiazepine Site of ,5-Containing GABAA Receptors.CHEMINFORM, Issue 38 2004Helen J. Szekeres Abstract For Abstract see ChemInform Abstract in Full Text. [source] Contribution of specific binding to the central benzodiazepine site to the brain concentrations of two novel benzodiazepine site ligandsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2007Andrew Pike Abstract The in vivo occupancy of brain benzodiazepine binding sites by compounds A and B was measured using a [3H]Ro 15-1788 binding assay and related to plasma and brain drug concentrations. The plasma concentration associated with 50% occupancy was higher for compound A than compound B (73 and 3.7 nM, respectively), however, there was little difference in the brain concentrations required (73 and 63 nM). Both compounds showed a non-linear relationship between plasma and brain concentrations such that above brain concentrations of ,100 nM increasing plasma concentrations did not result in a concomitant increase in brain concentrations. This is consistent with brain concentrations being dependent on a saturable compartment which was postulated to be the benzodiazepine binding site-containing GABAA receptors. This hypothesis was tested in ,1H101R mice, in which the ,1 subunit of the GABAA receptor is rendered insensitive to benzodiazepine binding resulting in an approximate 50% reduction in the total benzodiazepine-containing GABAA receptor population. It was shown that the Occ50 brain concentrations in the ,1H101R animals was lower (17 nM) than in wild type mice (63 nM), as was the plateau concentration in the brain (105 and 195 nM, respectively). These data suggest measured concentrations of compounds A and B in brain tissue are dependent on receptor expression with a minimal contribution from unbound and non-specifically bound compound. Copyright © 2007 John Wiley & Sons, Ltd. [source] In vivo detection of microglial activation in frontotemporal dementiaANNALS OF NEUROLOGY, Issue 6 2004Annachiara Cagnin MD Using positron emission tomography and [11C](R)-PK11195, a marker of "peripheral benzodiazepine sites" that is upregulated on activated microglia during progressive tissue pathology, we show increased binding of [11C](R)-PK11195 in frontotemporal lobar degeneration in the typically affected frontotemporal brain regions. This implies the presence of an active glial response reflecting progressive neuronal degeneration. It also suggests that increased [11C](R)-PK11195 binding, previously demonstrated for Alzheimer's disease, may occur independently from increased amyloid plaque formation, given that it is not a characteristic feature of frontotemporal lobar degeneration. Ann Neurol 2004;56:894,897 [source] Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autismAUTISM RESEARCH, Issue 4 2009A. Oblak Abstract The anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio-emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and gamma-amino-butyric acid (GABA) system may be affected in autism. The benzodiazepine binding site on the GABAA receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple-concentration ligand-binding study utilized 3H-muscimol and 3H-flunitrazepam to determine the number (Bmax), binding affinity (Kd), and distribution of GABAA receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABAA receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4%) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABAA receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio-emotional behaviors in autism. [source] | ||||||||||