Benzodiazepines 1 -labelled

Nitroaryl compounds Flunitrazepam Benzodiazepine Labels 50,000 MW polypeptide. Also autoradiographic localization in tissue slices (Mohler et al., 1980). 

Chiu, TH, Dryden, DM and Rosenberg, HC (1982) Kinetics of [ H]-labelled flunitrazepam binding to membrane-bound benzodiazepine receptors. Mol. Pharmacol. 21 57-65. 

This reaction was also carried out with 14C-labeled formic acid, leading to the radiochemically labeled s,-triazolo[4,3-a][ 1,4]benzodiazepine (58% yield).[153]... 

Specificity of Antibody binding of Chlordiazepoxide A good number of benzodiazepines are tested for their ability to complete with labelled chlordiazepoxide for the respective antibody binding site. The various competitors are adequately tested at a concentration of 200 ng i.e.., 10-times the concentration of chlordiazepoxide required to produce a 50% inhibition of binding as shown in Table 32.2. 

The basis for this technique lies in the competition between the test antigen and a labelled antigen for the available binding sites on a fixed amount of antibody. While the binding sites are traditionally associated with an antibody, any source of specific reversible binding sites may be used to create an assay in this format. Examples of such are specific transport proteins such as thyroxine-binding globulin and certain cellular receptors such as opiate or benzodiazepine receptors. Under these circumstances the equilibrium mixture may be represented thus ... 

Janssen, M.J., Ensing, K., de Zeeuw, R.A. A fluorescent receptor assay for benzodiazepines using coumarin-labeled desethylflumazenil as ligand. Anal. Chem. 2001, 73, 3168-3173. 

Some herbal preparations, particularly some unbranded Asian imports, have been found to contain inactive fillers or adulterants. In one assessmenf, 24% of imporfed herbs were found fo confain ingredienfs nof on fhe label. These included specific medicafions (aspirin, caffeine, diurefics, and even benzodiazepines), nof fo menfion heavy mefals, such as lead. Some Asian for-mulafions may also confain animal componenfs. Therefore, if is advisable fo buy only producfs fhaf lisf fhe following informafion bofanical name or names,... 

Figure 2 lists some other labelled compounds obtained by fluorodestannylation 4- and 6-p F]fluoro-/7 -tyramine [123], 2-[ F]fluoro-L-tyrosine [124], 2-[ F] oxoquazepam, an agonist of benzodiazepine receptors [125], 7-[ F]fluorota-crine, a potential agent for mapping acetylcholinesterase [126] and 2-[ F]fluoro-benzidine, a potential radioligand to image amyloid deposits in the brain [127]. 

A recent study found that cortical peripheral benzodiazepine receptors, as assessed with PET and [ C]PK11195, were increased by 30-40% in patients with AD when compared with healthy controls. This suggests active inflammatory processes in AD since PK11195 binds to activated microglia [72]. Several F-labeled tracers of the peripheral benzodiazepine receptor have been developed, and [i8p]PK14105 [73] and [i8p]FEDAA1106 [74] are the most well characterized. However, no reports have been published on the use of either of the two radiotracers in AD. The molecular structures of F-labeled tracers for the peripheral benzodiazepine receptor are shown in Fig. 5. 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

Fig. 4.4. Photoaffinity labeling of a benzodiazepine receptor. SDS-polyacrylamide gel electrophoresis of purified synaptic membranes after photoaffinity labeling with [3H]fluni-trazepam (3 nM). Right distribution of radioactivity in the gel. The hatched area is the label distribution when diazepam (10 pM) was present during photolysis (non-specific labeling). Left Coomassie blue staining pattern after irradiation (with and without diazepam present).

The use of click chemistry has also been applied to the synthesis of benzophe-none-modified y-secretase probes. The group of Yao reported the preparation of a compound library built up from Bpa-containing alkyne 77 and azide 78 (Fig. 7) [81]. The azide part contains a racemic hydroxyethylene moiety, and variations were made in its aryl sulfonamide domain. The compound library was screened for its potency against y-secretase inhibition and the most potent compounds were used to label active PS1 in a cell lysate. In addition, Fuwa and coworkers reported a divergent synthesis of y-secretase A/BPs by means of click chemistry with alkyne 79 and azide 80 [82]. Variations were made in the aryl part of the alkyne (dibenzoazepine or benzodiazepine) and in the type of spacer between the benzo-phenone moiety and biotin in the azide. PAL using these probes provided the authors with evidence that the molecular target of this type of probe is the N-terminal fragment of PS1. 

F-labelled benzhydrols 100 have been synthesized120 by the method of Sugasawa and coworkers121. Four different anilinochloroboranes have been prepared and coupled with [18F]-2-fluorobenzaldehyde in 70-90% yield after 10 minutes. The products 100 have been used to produce the corresponding [18F]-l,4-benzodiazepine-2-ones122. 

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