Benzodiazepine binding

A class of sedative/hypnotic type drug that exert their effects through the benzodiazepine binding site on GABAa receptors. The class consists both of molecules that contain the benzodiazepine moiety, for example diazepam, lorazepam and flunitrazepam, and the newer, non-benzodiazepine compounds such as zolpidem, zopiclone, indiplon and zaleplon. BzRAs are primarily used for the treatment of anxiety, insomnia and to elicit varying levels of sedation. The wide selection of compounds currently available affords the prescribing clinician extensive options in terms of relative efficacies and durations of action. 

Atack JR Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Curr Drug Target CNS Neurol Disord 2 213—232, 2003... 

Table 19.4 Putative endogenous ligands for the benzodiazepine binding domain on the GABAa receptor...

Awad, M and Gavish, M (1987) Binding of [ H]Ro 5-4864 and [ H]PK 11195 to cerebral cortex and peripheral tissues of various species species differences and heterogeneity in peripheral benzodiazepine binding sites. J. Neurochem. 49 1407-1414. 

Drugan, RC, Basile, AS, Crawley, JN, Paul, SM and Skolnick, P (1987) Peripheral benzodiazepine binding sites in the Maudsley Reactive rat selective decrease confined to peripheral tissues. Brain Res. Bull. 18 143-145. 

Duggan, MJ and Stephenson, FA (1988) Benzodiazepine binding site heterogeneity in the purified GABAa receptor. Eur. J. Pharmacol. 154 293-298. 

Churn, S. B., Rana, A., Lee, K. el al. (2002). Calcium/calmodulin-dependent kinase II phosphorylation of the GABAa receptor alphal subunit modulates benzodiazepine binding. J. Neurochem. 82, 1065-76. 

Sigel, E. Buhr, A. (1997). The benzodiazepine binding site of GABAA receptors. Trends Pharmacol. Sci. 18, 425-9. 

Amin, J., Brooks-Kayal, A., and Weiss, D. S. (1997) Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding and allosteric modulation of gamma-aminobutyric acidA receptors. Mol. Pharmacol. 51, 833-841. 

Boileau, A. J., Kucken, A. M Evers, A. R and Czajkowski, C. (1998) Molecular dissection of benzodiazepine binding and allosteric coupling using chimeric gamma-aminobutyric acidA receptor subunits. Mol. Pharmacol. 53, 295-303. 

Baureithel KH, Buter KB, Engesser A, Burkard W, Schaffner W. (1997). Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum. Pharm Acta Helv. 72(3) 153-7. 

Davies LP, Drew CA, Duffield P, Johnston GA, Jamieson DD. (1992). Kava pyrones and resin studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol. 71(2) 120-26. 

A series of tubes containing assay buffer (50 mM Tris/HCl, 150 mM KCl, pH 7.4), radioiabeiied benzodiazepine (typically 0-50 nM) and bovine brain membranes (final concentration 0.5 mg/ml or approximately 1 nM in benzodiazepine binding sites) is set up. Nonspecific binding is determined in the presence of an excess of unlabelled benzodiazepine. As some benzodiazepines are light sensitive, we usually use opaque amber tubes for these assays. 

Wieland HA, Luddens H, Seeburg PH. 1992. A single histidine in GABAa receptors is essential for benzodiazepine binding. J Biol Chem 267(3) 1426... 

Teissere JA, Czajkowski C. 2001. A p-strand in the y2 subunit lines the benzodiazepine binding site of the GABAa... 

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