GABA drug target

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

Schousboe, A, Sarup, A., Larsson, O. M. and White, H. S. GABA transporters as drug targets for modulation of GABAergic activity. Biochem. Pharmacol. 68 1557-1563. 

G-protein coupled receptor family comprises most well-known cell surface receptors including the major drug targets, as previously stated. Early PAL results have been reviewed in several papers, and book chapters. For opiate, NMDA, sigma, benzodiazepine, GABA, acetyl choline, and adrenerg, serotonine receptors see [52,59,60], and for purinerg, histamine, and dopamine receptors see [61]. 

Balfour DJ (2002) Neuroplasticity within the mesoaccumbens dopamine system and its role in tobacco Dependence, Curr Drug Targets CNS Neurol Disord 1 413-21 Balfour DJ (2004) The neurobiology of tobacco dependence a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6 899-912 Barik J, Wonnacott S (2006) Indirect modulation by alpha7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices interaction with glutamate and GABA systems and effect of nicotine withdrawal. Mol Pharmacol 69 618-628... 

Vacher CM, Bettler B. GABA(B) receptors as potential therapeutic targets. Curr Drug Targets CNS Neurol Disord. 2003 2 248-259. 

Johnsoton GA, Chebib M, Hanrahan JR, Mewett KN (2003) GABA(C) receptors as drug targets. 

Curr Drug Targets CNS Neurol Disord 2 260-268 Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M et al (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396 674-679... 

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... 

The reinforcing effects of opiate drugs involve a number of neuronal pathways [21]. In the VTA, opiates stimulate p-opioid receptors on GABA neurons that synapse on dopamine neurons. This inhibits the GABA neurons, leading to disinhibition of the dopamine neurons and enhanced dopamine release in the nucleus accumbens and other target areas (Fig. 56-3). Opiates also exert dopamine-independent effects in the nucleus accumbens by activating... 

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