Gamma-aminobutyric acid-A receptors

Bai, D., Zhu, G., Pennefather, P, Jackson, M. F., MacDonald, J. F., and Orser, B. A. (2001) Distinct functional and pharmacological properties of tonic and quantal inhibitory postsy-naptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons. Mol. Pharmacol. 59, 814-824. 

Rudolph, U., Crestani, F., Benke, D., Brunig, I., Benson, J. A., Fritschy, J. M., et al. (1999) Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor sub-types. Nature 401, 796-800. 

Kardos J, Blandl T. (1994). Inhibition of a gamma aminobutyric acid A receptor by caffeine. Neuroreport. 5(10) 1249-52. 

Clayton T, et al An updated unified pharmacophore model of the benzodiazepine binding site on gamma-aminobutyric acid(a) receptors Correlation with comparative models. Curr Med Chem 2007 14 2755. [PMID 18045122]... 

Siegwart R, Jurd R, Rudolph U Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3) gamma(2)gamma-aminobutyric acid(A) receptors. J Neurochem 2002 80 140. [PMID 11796752]... 

Kumar S, Fleming RL, Morrow AL. Ethanol regulation of gamma-aminobutyric acid A receptors genomic and nongenomic mechanisms. Pharmacol Ther. 2004 101 211-226. 

Kitamura A, Sato R, Marszalec W, et al. Halothane and propofol modulation of gamma-aminobutyric acid A receptor single-channel currents. Anesth Analg. 2004 99 409-415. 

Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (2000) Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors. Nature 403 274-80... 

Beckstead, M.J., J.L. Weiner, E.I. Eger II, D.H. Gong, and S.J. Mihic. Glycine and Gamma-aminobutyric acid(A) Receptor Function is Enhanced by Inhaled Drugs of Abuse. Molecular Pharmacology 57 (2000) 1199-1205. 

Boehm SL 2nd, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, Blednov YA, Harris RA. gamma-Aminobutyric acid A receptor subunit mutant mice new perspectives on alcohol actions. Biochem. Pharmacol. 2004 68 1581-1602. 

Massottti, M., Schlichting, J.L., Antonacd, M.D., Giusti, P., Memo, M., Costa, E., etal. (1991) Gamma-aminobutyric acid A receptor heterogeneity in rat central nervous system studies with clonazepam and other benzodiazepine Xtgz.t As,. Journal of Experimental Pharmacology and Therapeutics, 256, 1154—1160. 

Sapp, D.W., Witte, U., Turner, D.M., Longoni, B., Kokka, N. and Olsen, R.W. (1992) Regional variation in steroid anesthetic modulation of [35S] TBPS binding to gamma-aminobutyric acid-A receptors in rat htain.. Journal of Experimental Pharmacology and Therapeutics, 262, 801 08. 

DeLorey TM (1992) Gamma-aminobutyric acid A receptor structure and funetion. J. Biol. Chem. 267, 16747-16750. 

Gamma aminobutyric acid (GABA) receptors are located on the postsynaptic membranes of inhibitory synapses of both vertebrates and insects and contain within their membrane-spanning structure a chloride ion channel. They are found in both vertebrate brains and invertebrate cerebral ganglia (sometimes referred to as brains) as well as in insect muscles. Particular attention has been given to one form of this receptor—the GABA-A receptor—as a target for novel insecticides (Eldefrawi and Eldefrawi 1990). It is found both in insect muscle and vertebrate brain. The remainder of this description will be restricted to this form. 

GABA Gamma aminobutyric acid, a neurotransmitter. Acts upon GABA receptors located especially in the nervous system. 

So far attention has concentrated on the effects of lithium on excitatory transmitters. There is evidence that the drug can also facilitate inhibitory transmission, an effect that has been attributed to a desensitization of the pres)maptic gamma-aminobutyric acid (GABA) receptors, which results in an increase in the release of this inhibitory transmitter. The increased conversion of glutamate to GABA may also contribute to this process. Thus it would appear that lithium has a varied and complex action on central neurotransmission, the net result being a diminution in the activity of excitatory transmitters and an increase in GABAergic function. 

Pharmacology Eszopiclone is a nonbenzodiazepine hypnotic. The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is believed to result from its interaction with gamma-aminobutyric acid (GABA)-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors. 

Mechanism of Action A benzodiazepine that depresses all levels of the CNS, includ-ing limbic and reticular formation, by binding to benzodiazepine receptor sites on the gamma-aminobutyric acid (GABA) receptor complex. Modulates GABA, a major inhibitory neurotransmitter in the brain. Therapeutic Effect Produces anxiolytic 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]. 

Ethanol is a central nervous system (CNS) depressant that initially and selectively depresses some of the most active portions of the brain (reticular activity system and cortex). The mechanism of action most likely involves interference with ion transport at the axonal cell membrane rather than at the synapse, similar to the action of other anesthetic agents. Ethanol can bind directly to the gamma-aminobutyric acid (GABA) receptor in the CNS and cause... 

Brunig I, Sommer M, Hatt H, Bormann J. 1999. Dopamine receptor subtypes modulate olfactory bulb gamma-aminobutyric acid type receptors. Proc Natl Acad Sci US A 96 2456-2460. 

We have shown that the anthelmintics pyrantel, morantel and levamisole, activate acetylcholine (Ach) receptors on the muscle cell membranes of Ascaris suum and also that the avermectin 22,23-dihydroavermectin Bla (DHAVM) blocks the function of muscle cell gamma-aminobutyric acid (GABA) receptors. In experiments using micro-iontophoresis, the cholinergic anthelmintics were found to act directly on the muscle bag membrane, evoking a depolarizing response. 

Compound 24 is a gamma-aminobutyric acid (GABA) receptor modulator that interacts with the GABA-A sub-type which is, in turn, the same locale where the classical benzodiazepine anxiolytics are also thought to interact (diazepam or Valium being a common benzodiazepine structure shown above as 57). Although 24 is classed as a nonbenzodiazepine sedative-hypnotic because it has... 

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