Research Area
Neuropharmacology
Research Interests
Benzodiazepines, Molecular Structure, Receptors, GABA-A
Interest Group(s)
Grant(s)
Abstract
We are interested in the molecular structure of allosteric the binding sites present on GABA-A receptor subtypes, in the identification and pharmacology of subtype selective compounds and the molecular mechanisms behind so-called functional selectivity. We collaborate with Medicinal Chemists and Pharmacoinformatics groups, as well as pharmacologists whose research techniques complement ours.
Techniques
Expression of wild type and mutated recombinant GABA-A receptors in Xenopus laevis oocytes, HEK cells and other host cells, two electrode voltage clamp electrophysiology, radioligand binding assays; homology modelling, computational docking
Selected publications
- Varagic Z, Wimmer L, Schnuerch M, Mihovilovic MD, Huang S, Rallapalli S, Cook JM, Mirheydari P, Ecker GF, Sieghart W, Ernst M (2013) Identification of novel positive allosteric modulators and null modulators at the GABA-a receptor alpha+beta-interface Br J Pharmacol, 169(2): 371-383
- Varagic Z, Ramerstorfer J, Huang S, Rallapalli S, Sarto-Jackson I, Cook J, Sieghart W, Ernst M (2013) Subtype selectivity of alpha+beta-site ligands of GABA-A receptors - identification of the first highly specific positive modulators at alpha6beta2/3gamma2 receptors Br J Pharmacol, 169(2): 384-399
- Richter L, de Graaf C, Sieghart W, Varagic Z, Mörzinger M, de Esch IJP, Ecker GF, Ernst M (2012) Diazepam-bound GABA-A receptor models identify new benzodiazepine binding site ligands Nature Chem Biol, 8: 455-464
- Ramerstorfer J, Furtmüller R, Sarto-Jackson I, Varagic Z, Sieghart W, Ernst M (2011) The GABA-A receptor alpha+beta-interface: a novel target for subtype-selective drugs J Neurosci, 31: 870-877
- Sieghart W, Ernst M (2005) Heterogeneity of GABA-A receptors: revived interest in the development of subtype-selective drugs Curr Med Chem - Centr Nervous Syst, 5: 217-242
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