Diazepam receptors

Dmg receptors represent another type of receptor family. The central nervous system (CNS) effects of the anxiolytic, diazepam, and the psychotropic actions of the caimabiaoids and phencycUdine have resulted ia the identification of specific receptors for these molecules. This has resulted ia the search for an endogenous ligand for these receptors. Thus, ia these situations, the pharmacological action has preceded the discovery of the receptor which, ia turn, has provided clues ia several iastances to the endogenous ligand. 

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). 

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. 

GABAa receptors that contain the al, a2, a3, and a5 subunits in combination with (3 and y subunits can bind classical benzodiazepines, e.g., diazepam, whereas GABAa receptors that contain the a4 and a6 subunits do not bind classical benzodiazepines. Essentially, all benzodiazepines that are currently in clinical use bind indiscriminately to GABAa receptors that contain the... 

Benzodiazepines. Figure 3 Dissection of benzodiazepine pharmacology. The functional roles of GABAa receptor subtypes, mediating particular actions of diazepam, are indicated. A sign indicates that the respective response is mediated by the respective receptor subtype, a sign indicates that the respective response is apparently not mediated by the respective receptor subtype. ND = not determined. 

Tobler I, Kopp C, Deboer T et al (2001) Diazepam-induced changes in sleep role of the al GABAa receptor subtype. Proc Natl Acad Sci USA 98 6464 6469... 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Gray A, Allison C, Pratt JA A role for AMPA/kainate receptors in conditioned place preference induced by diazepam in the rat. Neurosci Lett 268 127-130, 1999... 

Moehler, H and Okada, T (1977) Properties of [3H]diazepam binding to benzodiazepine receptors in rat cerebral cortex. Life Sci. 20 2101-2110. 

Reddy, DS and Kulkarni, SK (1998) The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice. Psychopharmacology 137 391-100. 

As Shown in table 2, a comparative dose of 10 n units of PCP-like activity inhibited 3H-PCP binding in rat brain membranes, but did not inhibit binding of 3 H - d i hydromorphi ne, 3H - D - a 1 a2 - D -1 eu5-enkephalin, 3H-ethylketocyclazocine, 3H-diazepam, or -neurotensin. These results indicate that the active material is specific and selective from PCP receptors, as binding to the mu, delta, and kappa opioid receptors was unaffected, as was binding to benzodiazepine and neurotensin receptors. 

Compounds 227 and 232 were tested in vitro for inhibition of [3H]-diazepam-specific binding to benzodiazepine receptors in membranes from synaptosomes of rat brain and in vivo for their effects on conditioned behavior in rats (89FES29). 

The answer is b. (Hardman, pp 365—367J Benzodiazepines, such as diazepam, bind to the GABA receptor/ion channel complex, enhancing GABA-induced Cl" currents related to more frequent bursts of Cl channel opening by GABA. 

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