Diazepam displacement

Diazepam-displacing activity in human cerebrospinal fluid Diazepam-binding inhibitor (DBI)... 

Midazolam and diazepam decrease arterial pressure without a change ia heart rate. Like thiopeatoae, midazolam is a respiratory depressant. Advantages of midazolam are its amnestic effect, coupled with less postoperative depression (102). A reversal agent for the benzodiazepiaes has also become available. Flumazenil [78755-81-4] C25H24FN2O2, (5) displaces the beazodiazepiaes from their receptor but has Httie demoastrable activity of its owa (103,104). 

Electrophysiological studies show that benzodiazepines, barbiturates and sodium valproate facilitate GABAergic transmission in the animal brain. Further evidence comes from studies on the GABA-benzodiazepine receptor complex, the order of potency of a series of benzodiazepines to displace [3H] diazepam from its receptor site being clearly correlated with the antagonism of pentylenetetrazol seizures, but not with electroconvulsive seizures. However, most classes of anticonvulsants appear to facilitate... 

Ultrafiltration has been used to determine the protein bound fraction of many drags, such as methadone (Wilkins et al. 1997), phenylacetate and phenylbu-tyrate (Boudoulas et al. 1996), etoposide (Robieux et al. 1997), doxorubicin and vincristine (Mayer and St-Onge 1995), disopyramide (Echize et al. 1995), and ketamine and its active metabolites (Hijazi and Boulieu 2002). Schumacher et al. (2000) have shown the applicability for the determination of erythro-cyte/plasma distribution. The method of UF has been applied in the measurement of free unaltered thyroxin or after displacement by salicylate as well after displacement by heparin in healthy people and in patients with non-thyroidal somatic illness (Faber et al. 1993). The protein binding of tritium labeled, antidiabetic repaglinide and its displacement by warfarin, furosemide, tolbutamide, diazepam, glibenclamide and nicardipine were determined by ultrafiltration (Plumetal. 2000). 

The decreased plasma binding of sulfisoxazole in patients with diabetes is related to in vivo glycosylation of albumin, whereas the decreased plasma binding of diazepam may be caused by high concentrations of free fatty acid displacers. ... 

Valproate Carbamazepine epoxide Diazepam Felbamate Lamotrigine Phenobarbital Risk of toxicity, particularly with phenobarbital including primidone-derived phenobarbital and lamotrigine Inhibition of metabolism of the affected drug. Valproate also displaces diazepam from protein binding sites, affecting relation between total diazepam concentration and effect... 

Diazepam binding inhibitor (DBI) is a polypeptide with a molecular weight of 9 KD. It has been isolated from rat brain by monitoring its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the extracellular domain of the type A receptor for gamma-aminobutyric acid (GABAA receptor) and from mitochondrial BZD receptor located on the outer mitochondrial membrane. This peptide is known for multiple biological effects [109]. 

In order to make this point clear, we attempted to detect specific binding of [3h]DHP, [ H]muscimol and [3H]diazepam to EDTA-treated membranes under the same conditions as that for [3H]Pr-BP binding. Binding should decrease on addition of excess unlabeled ligands if a specific site existed. The binding of [3h]muscimol was reduced on addition of excess muscimol and GABA. Bicuculline methiodide was less potent in displacing [3H]muscimol (Table IV). 

The co-administration of carbamazepine can infrequently cause significant decreases in serum levels of some benzodiazepines (described with aiprazoiam and cionazepam). Vaiproate displaces diazepam from plasma protein binding and possibly inhibits its metabolism, leading to increased serum levels. A few studies have suggested that cbiordiazepoxide, cionazepam, and diazepam may elevate serum levels of pbenytoin. 

It was suggested that these changes occur because heparin displaces these drugs from their binding sites on the plasma albumins and that these changes in protein binding might possibly have some clinical consequences. For example, there could, theoretically, be sudden increases in sedation or respiratory depression because of the rapid increase in the active (free) fraction of diazepam. 

Radioligand displacement assays dominate this area, such as in the first MIP-based immunoassay reported by the group of Mosbach. Here, MIPs prepared against theophylline and diazepam, respectively, were shown to display comparable cross-reactivities to antibodies raised against the two drugs, with respect to a range of structural analogs. 

Davies, L.P., A.F. Cook, M. Poonian, and K.M. Taylor Displacement of pH] Diazepam Binding in Rat Brain by Dipyridamole and by 1-Methylisoguanosine, a Marine Natural Product with Muscle Relaxant Activity. Life Sci. 26, 1089 (1980). 

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