Journal
CURRENT MEDICINAL CHEMISTRY
Volume 14, Issue 26, Pages 2755-2775Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/092986707782360097
Keywords
aminobutyric acid(A) receptors; gated ion channels; GABA-A; computer-assisted analysis; benzodiazepine
Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH [R03MH061450, R01MH046851] Funding Source: NIH RePORTER
- NIMH NIH HHS [R03 MH061450, MH46851] Funding Source: Medline
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A successful unified pharmacophore/receptor model which has guided the synthesis of subtype selective compounds is reviewed in light of recent developments both in ligand synthesis and structural studies of the binding site itself. The evaluation of experimental data in combination with a comparative model of the alpha 1 beta 2 gamma 2 GABA(A) receptor leads to an orientation of the pharmacophore model within the Bz BS. Results not only are important for the rational design of selective ligands, but also for the identification and evaluation of possible roles which specific residues may have within the benzodiazepine binding pocket.
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