The Molecular Pharmacology team within the Vanderbilt Center for Neuroscience Drug Discovery supports assay development, high-throughput screening, and detailed in vitro pharmacology analysis of ligands with the goal of developing therapeutics, specifically for central nervous system disorders. We interface closely with all areas of the VCNDD, including chemistry, in vitro and in vivo drug metabolism and pharmacokinetics, and in vivo pharmacology. In addition to our drug discovery efforts, we also work closely with the more basic science aspects of the Conn Laboratory, as the development of better tool compounds allows us to deeply explore the biology of our targets. The main focus of the group is the discovery and characterization of allosteric modulators of metabotropic glutamate and muscarinic receptors; in addition, we have also developed assays for measuring transporter activity to detect inhibitors of Glycine Transporter 1 (GlyT1), a possible mechanism being explored for the treatment of schizophrenia.
The majority of the current assays we employ are cell based fluorescence assays to detect allosteric modulators of 7-Transmembrane Spanning (7-TM) or G-Protein Coupled Receptors (GPCRs). These assays include calcium mobilization assays as well as a method developed within the group that monitors the flux of the ion thallium through G Protein Regulated Inwardly Rectifying Potassium (GIRK) channels (Niswender et. al., 2008).