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 disorders. 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, and
- Development of a model system in C. elegans to identify new targets for drugs to treat psychoses and mood disorders.
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
- Cécile Béguin, Ph.D. - Assistant Professor
- Ned Buttner, M.D., Ph.D. - Assistant Research Neurologist
- Elena Chartoff, Ph.D. - Assistant Professor
- Diane Damez-Werno, M.S. - Research Fellow
- Sarah Demarco - Research Assistant (e-mail)
- Katherine Duncan - Technical Research Assistant (e-mail)
- David Eyerman, Ph.D. - Research Fellow (e-mail)
- Rakesh Karmacharya, M.D., Ph.D. - Assistant Psychiatrist & Research Fellow
- Nicholas Lange, Sc.D. - Associate Professor (e-mail)
- Emily Menesale - Technical Research Assistant (e-mail)
- Thomas Munro, Ph.D. - Research Fellow
- Donna McPhie, Ph.D. - Instructor
- Angelica Ortiz - Research Assistant (e-mail)
- David Potter, M.A. - Senior Technical Research Assistant (e-mail)
- Steven Punzell - Research Assistant (e-mail)
- Gregory Sliwoski - Research Assistant (e-mail)
- Nancy Ye, M.A.- Research Associate (e-mail)
- Ma J, Ye N, Lange N, Cohen BM. Dynorphinergic GABA neurons are a target of both typical and atypical antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus and thalamic central medial nucleus. Neuroscience 121(4):991-998, 2003.
- Cohen BM, Cherkerzian S, Ma J, Ye N, Wager C, Lange N. Cells in midline thalamus, central amygdala and nucleus accumbens responding specifically to antipsychotic drugs. Psychopharmacology 167(4):403-410, 2003.
- Béguin C, Richards MR, Wang Y, Chen Y, Liu-Chen LY, Ma Z, Lee DYW, Carlezon WA, Cohen BM. Synthesis and in vitro pharmacological evaluation of salvinorin A analogues modified at C(2). Bioorganic & Medicinal Chemistry Letters 15(11):2761–2765, 2005. (download as a PDF / republished with permission from Elsevier - original article here)
- BĂ©guin C, Richards MR, Li J-G, Wang Y, Xu W, Liu-Chen L-Y, Carlezon WA, Jr, Cohen BM. Synthesis and in vitro evaluation of salvinorin A analogues: Effect of configuration at C(2) and substitution at C(18). BMCL 16:4679-4685, 2006.
- Ma J, Ye N, Cohen BM. Expression of noradrenergic alpha1, serotoninergic 5HT2a and dopaminergic D2 receptors on neurons activated by typical and atypical antipsychotic drugs. Prog Neuro-Psychopharmacol. Biol. Psychiatry 30:647-657, 2006.
- Ma J, Cohen BM. Typical and atypical antipsychotic drugs target DARPP-32 and neurotensin-containing neurons, but not GABAergic interneurons and substance P-containing neurons in the shell of nucleus accumbens of ventral striatum. Neurosci 141:1469-1480, 2006.
- Munro TA, Duncan KK, Staples RJ, Xu W, Liu-Chen L-Y, BĂ©guin C, Carlezon Jr WA, Cohen BM. 8-epi-Salvinorin B: crystal structure and affinity at the k opioid receptor. Beilstein Journal of Organic Chemistry 3:1, 2007.
- Karmacharya R, Lundy MY, Silwoski GR, Cohen BM, Buttner EA. Identification of clozapine effects on the insulin-signaling pathway in Caenorhabditis elegans. Submitted, 2007.
- BĂ©guin C, Cohen BM. Medicinal chemistry of kappa opioid receptor antagonists. In: Dean RL III, Bilsky EJ, Negus SS III (eds), Opioid Receptors and Antagonists: From Bench to Clinic. Humana Press, Totowa, New Jersey. Submitted, 2006.
- 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. Submitted, 2007.
- Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen L-Y, Carlezon WA, Jr, Cohen BM, BĂ©guin C. Standard protecting groups create potent and selective kappa opioids: Salvinorin B alkoxymethyl ethers. Submitted, 2007.
- BĂ©guin 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. C-2 modified salvinorin analogues: identification of a highly potent and selective kappa opioid receptor agonist with improved metabolic stability and in vivo efficacy. Submited, 2007.
Our work is supported by NIH grants, the
Stanley Medical Research Institute,
NARSAD, industrial contracts, and private gifts.
01.2008
