Benzodiazepine receptors binding sites

Ghose AK, Crippen GM. Modeling the benzodiazepine receptor binding site by the general three-dimensional structure-directed quantitative structure-activity relationship method REMOTEDISC. Mol Pharmacol 1990 37 725-734. 

A. K. Ghose and G. M. Crippen, Mol. Pharmacol., 37, 725 (1990). Modeling the Benzodiazepine Receptor Binding Site by the General Three-Dimensional Structure-Directed Quantitative Structure-Activity Relationship Method REMOTEDISC. 

FIGURE 8—19. The GABA A receptor is shown here. It acts as a gatekeeper for a chloride channel. It also has a key allosteric modulatory site nearby, known as the benzodiazepine (BZ) binding site. 

Clonazepam, U5P. Clonazepam S-(2-chlorophenyl)-3-dihydro-7-nitro-2//-1,4-benzodiazpin-2-one (iCIonopin). partially selective at benzodiazepine allosteric binding sites on GABAa receptors, is useful in ab.sence seizures and in myoclonic seizures. Tolerance to the anticonvulsant effect often develops, a common problem with the benzodiazepines. Metabolism involves hydroxylation of the 3 position, followed by glucuronidation and nitro group reduction, followed by acetylation. 

It is a partial against at benzodiazepine allosteric binding sites on GABA receptors. The... 

This tissue preparation contrasts with that used to prepare membranes for benzodiazepine receptor binding vide supra) wherein no detergent treatment was necessary nor did the tissue have to be frozen prior to assay. In most cases, tissue can be used for receptor binding assays over extended periods of time if stored frozen. However, some receptor binding procedures, such as that used to measure the serotonin2 site, require that the tissue be used within 24 hr of preparation. 

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. 

The binding site for barbiturates on the GABAa receptor is less well defined. Barbiturates act by increasing the conductance level. In contrast to benzodiazepines, they also display direct agonistic action on GABAa receptors. Also in contrast to... 

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

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

False neurotransmitters resulting from increased levels of aromatic amino acids, high levels of y-aminobutyric acid, and endogenous benzodiazepines have also been implicated in HE. These substances bind to both the y-aminobutyric acid and benzodiazepine receptors and act as agonists at the active receptor sites.20... 

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