GABA-benzodiazepine receptor

De Bias AL, Vitorica J, Friedrich P (1988) Localization of the GABA, receptor in the rat brain with a monoclonal antibody to the 57,000 M peptide of the GABA receptor/benzodiazepine receptor/Cl channel complex. J. Neurosci., 8, 602-614. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

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

The undisputed efficacy of benzodiazepines in relief of anxiety led to the question of whether this disorder could arise from abnormal concentrations in the brain of an endogenous ligand or a malfunction of the benzodiazepine/GABA receptor system. An important study, aimed at distinguishing between these possibilities, has been carried out in humans (Nutt et al. 1990) and was based on the premise that anxiety could be caused by either ... 

Malizia, AL, Cunningham, VJ, Bell, CJ, Liddle, PF, Jones, T and Nutt, DJ (1998) Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder preliminary results from a quantitative PET study. Arch. Gen. Psychiatry 55 715-720. 

This area has been covered in a review by Eldefrawi and Eldefrawi [23]. The GABA -receptor channel is activated by GABA (Fig. 2), avermectin, muscimol, taurine (Fig. 2) and j -alanine (Fig. 2). The activation by agonists is potentiated by benzodiazepines and barbiturates. The channel is blocked by the competitive... 

Niles, L. (1991). Melatonin interaction with the benzodiazepine-GABA receptor complex in the CNS. Adv. Exp. Med. Biol. 294, 267-77. 

Erker and Trinkl synthesized the tricycles 177 as novel GABA-A/benzodiazepine receptor ligands via synthesis of enol phosphates such as 175 and reaction with isocyanides 176 (Scheme 13) <2001H1963>. 

Baraldi M, Guidotti A, Schwartz JP, Costa E GABA receptors in clonal cell lines A model for study of benzodiazepine action at molecular level. Science 1979 205 821-823. 

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. 

Further, the removal of benzodiazepine sensitivity in a selective a subunit in a mouse using the gene knockin technique has established that the al subunit plays a major role in the sedative and amnesiac effects of benzodiazepines, part of the anticonvulsant effect and little of the anxiolytic effect the latter effects are more importantly mediated by the a2 subunit [5, 6], The 0 subunit selectivity for the drugs loreclezole (an anxiolytic) and etomidate (an anesthetic) allowed determination that a single residue in the M2 domain could account for this selectivity (02 = 03 >01). When a mouse knockin selectively removed the etomidate sensitivity of the 02 subunit, the animals showed reduced sensitivity to sedative effects of etomidate but no reduction of the true anesthetic effects. In contrast, mutation of the 03 subunit to negate etomidate sensitivity of that subunit alone resulted in a mouse with no sensitivity to the anesthesia produced by etomidate. This proved that the GABA receptor is the target of at least this one anesthetic (etomidate) and, furthermore, that the specific locations in the brain of 03 subunits are important for anesthetic action, while the... 

---