GABA receptors and transporters
The main inhibitory neurotransmitter γ-aminobutyric acid (GABA) exerts its effect in the central nervous system through two distinct classes of receptors: ionotropic GABAA and GABAC receptors and the metabotropic GABAB receptors. The effect of GABA is terminated by an efficient reuptake/transporter system. The GABA receptor system is involved in a range of physiological functions, and has considerable interest as therapeutic targets in the treatment of a number of neurodegenerative and psychiatric disorders.
Both the different GABA-transporters and the GABA receptor classes and subtypes of these display different pharmacology and regional distribution, which underlines the need for development of selective ligands.
Contact persons
Further reading
GABA-A-receptoren: Bedre modeller – bedre lægemidler, Lægemiddelforskning, 2010 (in Danish)
Effekt og bivirkninger: GABA fra A til C, Lægemiddelforskning, 2006 (in Danish)
Key references
Sander, T, Frølund, B., Bruun, A.T., Ivanov, I., McCammon, J.A., Balle, T., new insights into the GABAA receptor structure and orthosteric ligand binding: Receptor modelling guided by experimental data, Proteins, 2011, 79, 1458–1477.
Møller, H.A., Sander, T., Kristensen, J.L., Nielsen, B., Krall, J., Bergmann, M.L., Christiansen, B., Balle, T., Jensen, A.J., Frølund, B. Novel 4-(Piperidin-4-yl)-1-hydroxypyrazoles as g-Aminobutyric Acid-A Receptor Ligands: Synthesis, Pharmacology, and Structure-activity Relationships., J. Med. Chem., 2010, 53, 3417–3421.
Madsen, C; Jensen, A.J.; Liljefors, T.; Kristiansen, U.; Nielsen, B.; Hansen, C.P.; Larsen, M.; Ebert, B.; Bang-Andersen, B.; Krogsgaard-Larsen, P.; Frølund, B. 5-Substituted Imidazole-4-acetic acid analogues: Synthesis, Modeling and Pharmacological Characterization of a Series of Novel γ-aminobutyric acidC Receptor Agonists. J.Med.Chem., 2007, 15, 4147–4161
Collaborators
Associate Professor Thomas Balle, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen.
Associate Professor Uffe Kristiansen, Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Copenhagen.
Bjarke Ebert, Department of molecular pharmacology, H. Lundbeck A/S, Denmark.
Professor Arne Schousboe, Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Copenhagen.
Professor Steven White, Department of Pharmacology, University of Utah, Salt Lake City.
Professor Trevor Smart, Department of Pharmacology, University College London
Associate Professor Mary Chebib, Faculty of Pharmacy, University of Sydney
