MAILMAN RESEARCH CENTER
Molecular Pharmacology Laboratory
The Molecular Pharmacology Laboratory Staff
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The investigators in the Molecular Pharmacology Laboratory study the mechanisms of action of currently available medications for Bipolar Disorders and Schizophrenia and work to identify new targets and new compounds to treat these and other neuropsychiatric disorders, including mood, anxiety, and psychotic disorders and dementias. Particular areas of recent or current research include:
- Characterizing the mechanisms by which cells and circuits in the brain respond to antipsychotic and mood stabilizing agents;
- The synthesis and testing of agents which modulate activity at brain kappa and trace amine receptors;
- Development of a model system in C. elegans to identify new targets for drugs to treat psychoses and mood disorders;
- Glial and glutamate dysfunction models of mood disorders; and
- Repair or regeneration of neurons and glia in models of neurodegenerative disorders.
Hypothesis: Dysregulating glial glutamatergic transmission can induce anhedonia or dysphoria, prominent symptoms of depression.
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Dynorphinergic cells are activated by clozapine
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Synthesis of Salvinorin Analogues Modified at the C-2 Position
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Time-course study of larval arrest (wt N2 strain) in the presence of clozapine.
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Core Personnel and Associated Faculty
- Bruce M. Cohen, M.D., Ph.D. - Director
- Anita Bechtholt-Gompf, Ph.D., Instructor
- Cécile Béguin, Ph.D. - Assistant Professor
- Ned Buttner, M.D., Ph.D. - Assistant Research Neurologist
- Elena Chartoff, Ph.D. - Assistant Professor
- Sarah Elmiligy - Technical Research Assistant (e-mail)
- Rakesh Karmacharya, M.D., Ph.D. - Assistant Psychiatrist & Research Fellow
- Nicholas Lange, Sc.D. - Associate Professor (e-mail)
- Thomas Munro, Ph.D. - Research Fellow
- Donna McPhie, Ph.D. - Instructor
- David Potter, M.A. - Senior Technical Research Assistant (e-mail)
- Justin Potuzak, Ph. D. - Assistant Professor
- Laura Sargent - Technical Research Assistant
- Kai Sonntag, M.D., Ph.D. - Assistant Professor
- Jon Wong - Senior Technical Research Assistant
- Nancy Ye, M.A.- Research Associate (e-mail)
- Munro TA, Duncan KK, Staples RJ, Xu W, Liu-Chen L-Y, Béguin C, Carlezon Jr WA, Cohen BM. 8-epi-Salvinorin B: crystal structure and affinity at the kappa opioid receptor. Beilstein Journal of Organic Chemistry 3:1, 2007.
- Béguin C, Potter DN, DiNieri JA, Munro TA, Richards MR, Paine TA, Berry L, Zhao Z, Roth BL, Xu W, Liu-Chen L-Y, Carlezon WA Jr, Cohen BM. N-methylacetamide analogue of salvinorin A: a highly potent and selective kappa opioid receptor agonist with oral efficacy. J Pharmacology Exp Ther: 324(1): 188-95, 2008.
- Chartoff EH, Potter D, Damez-Werno D, Cohen BM, Carlezon WA, Jr. Exposure to the selective kappa opioid salvinorin A modulates the behavioral and molecular effects of cocaine in rats. Neuropsychopharmacology 33(11): 2676-2687, 2008.
- Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen L-Y, Carlezon WA, Jr, Cohen BM, Béguin C. Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers. Bioorg Med Chem 16(3): 1279-86, 2008.
- Béguin C. Duncan KK, Munro TA, Ho DM, Xu W, Liu-Chen LY, Carlezon WA Jr, Cohen BM. Modification of the furan ring of salvinorin A: Identification of a selective partial agonist at the kappa opioid receptor. Bioorg Med Chem 17(3): 1370-1380, 2009.
- Karmacharya R, Sliwoski GR, Lundy MY, Cohen BM, Buttner EA. Clozapine interaction with phosphatidyl inositol 3-kinase (PI3K)/insulin-signaling pathway in Caenorhabditis elegans. Neuropsychopharmacology 34(8): 1968-78, 2009. (Featured Paper)
- Carlezon WA Jr, Béguin C, Knoll AT, Cohen BM. Kappa-opioid ligands in the study and treatment of mood disorders. Pharmacol Ther 123(3): 334-43, 2009.
- Hooker JM, Munro TA, Béguin C, Alexoff D, Shea C, Xu Y, Cohen BM. Salvinorin A and derivatives: protection from metabolism does not prolong short term whole brain residence. Neuropharmacology 57(4): 386-91, 2009.
- Cataldo AM, McPhie DL, Lange NT, Punzell S, Ye NZ, Froimowitz MP, Hassinger LC, Menesale EB, Cohen BM. Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J of Pathology, in press, 2010.
- Nemeth CL, Paine TA,Rittiner JE, Béguin C, Carroll FI, Roth BL, Cohen BM, Carlezon WA Jr. Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. In press, Psychopharmacology, 2010.
Our work is supported by NIH grants, NARSAD and other foundation awards, industrial contracts, and private gifts.
04.2010
