PRINCIPAL INVESTIGATORS

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Amy Hauck Newman, Ph.D., Deputy Scientific Director

Chief, Molecular Targets and Medications Discovery Branch
Chief, Medicinal Chemistry Section

Post-doctoral Training - Laboratory of Medicinal Chemistry, NIDDK, NIH (advisor: Dr. Kenner C. Rice)

Ph. D. - Medicinal Chemistry, Medical College of Virginia, Virginia Commonwealth University (thesis advisor: Dr. Richard Glennon)

B.S. - Chemistry, Mary Washington College

RESEARCH INTERESTS

Our research effort is focused on the design and synthesis of novel ligands to study the function of selected G-protein coupled receptors and monoamine transporters in the central nervous system. Highly selective compounds are designed and synthesized for characterization of these molecular targets and to develop structure-activity relationships. In addition, specific tools such as fluorescent and radiolabeled ligands are synthesized for receptor or transporter structure-function studies. My research program is currently studying the dopamine and serotonin transport systems and the dopamine D2 receptor family (D2/D3) through the design, synthesis and pharmacological evaluation of novel ligands. The combination of state of the art synthetic organic chemistry techniques with molecular modeling and interpretation of pharmacological data has resulted in the discovery of important molecular probes for studying these neurochemical targets. It is envisioned that, ultimately, this multidisciplinary approach will provide new leads toward the development of potential pharmacotherapeutic agents for the treatment of addiction.

Selected Publications:

1. Loland, C. J.; Mereu, M.; Okunola, O. M.; Cao, J.; Prisinzano, T. E.; Kopajtic, T.; Shi, L.; Katz, J. L.; Tanda, G.; Newman, A. H. R-Modafinil (Armodafinil): A Unique Dopamine Uptake Inhibitor and Potential Medication for Psychostimulant Abuse. Biol. Psychiatry, 2012, 72, 405-413. Featured Article and September 2012 Issue cover.

2. Newman, A. H.; Beuming, T.; Banala, A.; Donthamsetti, P.; Pongetti, K.; LaBounty, A.; Levy, B.; Cao, J.; Michino, M.; Luedtke, R. R.; Javitch, J. A.; Shi, L. Molecular Determinants of Selectivity and Efficacy at the Dopamine D3 Receptor (D3R). J. Med. Chem. 2012, 55, 6689-6699. Featured Article and August Issue cover.

3. Newman, A. H.; Blaylock, B. L.; Nader, M. A. Bergman, J. Sibley, D. R.; Skolnick, P. Medication Discovery for Addiction: Translating the Dopamine D3 Receptor Hypothesis. Biochemical Pharmacology, 2012, 84 (7) 882-890. Invited Commentary.

4. Plenge, P.; Shi, L.; Beuming, T.; Newman, A. H.; Weinstein, H.; Gether, U.; Loland, C. J. The allosteric binding site for antidepressants in the serotonin transporter is located to the conserved extracellular vestibule. J. Biol. Chem. 2012, 287 (47) 39316-39326.

5. Keck, T. M.; Zou, M.-F.; Zhang, P.; Rutledge, R. P.; Newman A. H. Metabotropic glutamate receptor 5 negative allosteric modulators as novel tools for in vivo investigation. ACS Med. Chem. Lett. 2012, 3 (7), 544-549.

6. Wildling, L.; Rankl, C.; Haselgrubler, T.; Gruber, H. J.; Holy, M.; Newman, A. H.; Zou, M.-F.; Freissmuth, M.; Sitte, H. H.; Hinterdorfer, P. Probing the binding pocket of the serotonin transporter by single molecular force spectroscopy on living cells. J. Biol. Chem., 2012, 287 (1) 105-113.

7. Banala, A. K.; Levy, B. A.; Khatri, S. S.; Mishra, Y.; Griffin, S. A.; Luedtke, R. R.; Newman, A. H. N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl) piperazine-1-yl)-butyl)-aryl carboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity. J. Med. Chem. 2011, 54 (10) 3581-3694.

8. Chien, E. Y. T.; Liu, W.; Zhao, Q.; Katritch, V.; Hanson, M. A.; Shi, L.; Newman, A. H.; Javitch, J. A.; Cherezov, V.; Stevens, R. C. Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist. Science, 2010, 3330, 1091-1095.

9. Newman, A. H.; Grundt, P.; Cyriac, G.; Deschamps, J. R.; Taylor, M.; Kumar, R.; Ho, D.; Luedtke, R. R. N-(4-(4-(2,3-Dichloro- or 2-methoxyphenyl)piperazin-1-yl)-butyl)-heterobiarylcarboxamides with Functionalized Linking Chains as High Affinity and Enantioselective D3 Receptor Antagonists. J. Med. Chem. 2009, 52 (8), 2559-2570.

10. Beuming, T.; Bergmann, M. L.; Shi, L.; Gracia, L.; Raniszewska, K.; Newman, A. H.; Javitch, J. A.; Weinstein, H.; Gether, U.; Loland, C. J. Mapping of the Binding Sites for Cocaine and Dopamine in the Dopamine Transporter. Nature Neurosci. 2008, 11(7), 780-789.

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