Research Topics
| Bryan RothSummaryAffiliation: Case Western Reserve University Country: USA Publications
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Publications
Progress towards better understanding and treatment of major psychiatric illnessesAtheir Abbas
Case Western Reserve University, Department of Biochemistry, 2109 Adelbert Road, Cleveland, OH 44106, USA
Drug Discov Today 10:960-2. 2005- Molecular and cellular mechanisms for the polarized sorting of serotonin receptors: relevance for genesis and treatment of psychosisBryan L Roth
Department of Biochemistry and National Institute of Mental Health Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
Crit Rev Neurobiol 16:229-36. 2004..Uncovering the processes responsible for the polarization of 5-HT2A receptors to neuronal subdomains will likely provide crucial insights into the modulating mechanisms that can affect human cognition and perception... - Receptor systems: will mining the receptorome yield novel targets for pharmacotherapy?Bryan L Roth
Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
Pharmacol Ther 108:59-64. 2005..Case histories of receptorome-based discovery efforts are then highlighted and the relevance of this approach to the discovery and validation of molecular targets for drug abuse treatment is emphasized... - Screening the receptorome yields validated molecular targets for drug discoveryBryan L Roth
Department of Biochemistry, Case Comprehensive Cancer Center, National Institute of Mental Health Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
Curr Pharm Des 12:1785-95. 2006..Additionally, we will provide evidence that receptorome-based screening provides insights into novel therapeutic indications of approved medications and serves to validate targets for therapeutic drug discovery... - Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disordersBryan L Roth
Department of Biochemistry, and NIMH Psychoactive Drug Screening Program, Case Western Reserve University Medical School, 2109 Adelbert Road, Cleveland, OH 44106, USA
Psychopharmacology (Berl) 174:17-24. 2004..This review provides evidence for and against the use of selective 5-HT receptor drugs as cognition enhancing agents for schizophrenia and other disorders... - Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discoveryBryan L Roth
National Institute of Mental Health Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
Pharmacol Ther 102:99-110. 2004..Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies... - Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophreniaBryan L Roth
Department of Biochemistry, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, Cleveland, Ohio 44106, USA
Nat Rev Drug Discov 3:353-9. 2004 - Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compoundDavid N Wald
Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106, USA
Cancer Res 68:4369-76. 2008..Besides in vitro activity, 6BT also shows the ability to impair HL-60 and MV4-11 tumor growth in nude mice. 6BT is a promising new monocytic differentiation agent with apparent leukemic cell-specific activity... - Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disordersAtheir Abbas
Case Western Reserve University School of Medicine, Biochemistry, Cleveland, OH 44106, USA
Expert Opin Pharmacother 9:3251-9. 2008..Pimavanserin is also being evaluated as a possible anti-insomnia drug... - Screening the receptorome: an efficient approach for drug discovery and target validationRyan T Strachan
Department of Biochemistry, Comprehensive Cancer Center and NIMH Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
Drug Discov Today 11:708-16. 2006..Receptorome screening has also been used to discover, and thereby avoid, the molecular targets responsible for serious and unforeseen drug side effects... - PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptorsAtheir I Abbas
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
J Neurosci 29:7124-36. 2009..These results demonstrate that PSD-95, in addition to the well known role it plays in scaffolding macromolecular glutamatergic signaling complexes, profoundly modulates metabotropic 5-HT(2A) and 5-HT(2C) receptor function... - Screening the receptorome for plant-based psychoactive compoundsBryan L Roth
Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106-4935, USA
Life Sci 78:506-11. 2005.... - Finding new tricks for old drugs: an efficient route for public-sector drug discoveryBryan L Roth
Department of Biochemistry, Comprehensive Cancer Center and National Institute of Mental Health Psychoactive Drug Screening Program, 2109 Adelbert Road, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
Nat Rev Drug Discov 4:1005-14. 2005..This approach has also led to the discovery of the molecular targets responsible for serious drug side effects, thereby allowing efficient 'counter-screening' to avoid these side effects... - Salvinorin A: from natural product to human therapeuticsTimothy A Vortherms
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
Mol Interv 6:257-65. 2006..The discovery of KOR as the molecular target of salvinorin A has opened up many opportunities for drug discovery and drug development for a number of psychiatric and non-psychiatric disorders... - H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugsWesley K Kroeze
Department of Biochemistry, RM W463, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4935, USA
Neuropsychopharmacology 28:519-26. 2003.... - Screening the receptoromeWesley K Kroeze
Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
J Psychopharmacol 20:41-6. 2006.... - Contributions of molecular biology to antipsychotic drug discovery: promises fulfilled or unfulfilled?Bryan L Roth
Department of Biochemistry, National Institute of Mental Health Psychoactive Drug Screening Program, Case Western Reserve University Medical School, Cleveland, Ohio, USA
Dialogues Clin Neurosci 8:303-9. 2006..It is suggested, instead, that drugs which interact with a multiplicity of molecular targets are likely to show greater efficacy in treating the core symptoms of schizophrenia... - The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions?Marilyn A Davies
Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
Psychopharmacology (Berl) 178:451-60. 2005..Thus, these results are consistent with the notion that a balanced degree of activity at multiple biogenic amine receptors, including M(1) muscarinic agonism, is responsible for the uniquely beneficial actions of clozapine... - Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivoAtheir I Abbas
Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
Psychopharmacology (Berl) 205:119-28. 2009.... - Receptorome screening for CNS drug discoveryTimothy A Vortherms
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4935, USA
IDrugs 8:491-6. 2005..This commentary will describe discovery-based approaches and provide several recent examples of novel ligand-receptor interactions discovered through systematic screening of the 'receptorome'... - Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence affect plasma membrane targeting, ligand binding, and calcium influx in heterologous mammalian cellsPhillip L Quirk
Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4965, USA
J Neurosci Res 77:498-506. 2004..Furthermore, we demonstrate that each site is necessary for 5-HT3(A)R-mediated Ca(2+) influx. We conclude that N-glycosylation is a critical step in the maturation, trafficking, and function of the murine 5-HT3(A)R... - 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitroVincent Setola
Department of Biochemistry, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106 4935, USA
Mol Pharmacol 63:1223-9. 2003..These findings also underscore the necessity of screening current and future drugs at h5-HT2B receptors for agonist actions before their use in humans... - Caveolin-1 interacts with 5-HT2A serotonin receptors and profoundly modulates the signaling of selected Galphaq-coupled protein receptorsAnushree Bhatnagar
Department of Biochemistry, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA
J Biol Chem 279:34614-23. 2004..These studies provide compelling evidence for a prominent role of Cav-1 in regulating the functional activity of not only 5-HT(2A) serotonin receptors but also selected Galpha(q)-coupled receptors... - The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT(2A) receptor induces agonist-independent internalizationJohn A Gray
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4935, USA
Mol Pharmacol 63:961-72. 2003..This is the first demonstration that a constitutively active arrestin mutant can both induce agonist-independent internalization and stabilize the agonist-high affinity state of an arrestin-insensitive G protein coupled receptor... - G-protein-coupled receptors at a glanceWesley K Kroeze
Departments of Biochemistry, Neurosciences and Psychiatry, NIMH Psychoactive Drug Screening Program, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA
J Cell Sci 116:4867-9. 2003 - Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitizationJohn A Gray
Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Biochemistry 42:10853-62. 2003..Taken together, these findings indicate that the process of agonist-mediated desensitization of 5-HT(2A) receptors requires the presence of two nonconserved serine residues located in distinct intracellular loops... - Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacologyDavid A Shapiro
Department of Biochemistry, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, OH 44106-4935, USA
Neuropsychopharmacology 28:1400-11. 2003.... - Evidence for a model of agonist-induced activation of 5-hydroxytryptamine 2A serotonin receptors that involves the disruption of a strong ionic interaction between helices 3 and 6David A Shapiro
Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106 4935, USA
J Biol Chem 277:11441-9. 2002..L. Roth and D. A. Shapiro (2001) Expert Opin. Ther. Targets 5, 685-695) and others, that this may represent a general mechanism of activation for many, but not all, G-protein-coupled receptors... - Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessmentXi Ping Huang
Department of Pharmacology, University of North Carolina Chapel Hill, School of Medicine, Chapel Hill, North Carolina 27514, USA
Mol Pharmacol 76:710-22. 2009..Taken together, our data demonstrate that patterns of 5-HT(2B) receptor functional selectivity might be useful for identifying compounds likely to induce valvular heart disease... - p90 Ribosomal S6 kinase 2, a novel GPCR kinase, is required for growth factor-mediated attenuation of GPCR signalingRyan T Strachan
Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
Biochemistry 49:2657-71. 2010..g., neuropsychiatric and neurodevelopmental disorders)... - p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signalingDouglas J Sheffler
Departments of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Proc Natl Acad Sci U S A 103:4717-22. 2006..Because RSK2-inactivating mutations in humans lead to Coffin-Lowry syndrome, our results imply that alterations in GPCR signaling may account for some of its clinical manifestations... - Arresting serotoninAtheir Abbas
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Proc Natl Acad Sci U S A 105:831-2. 2008 - Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligandBlaine N Armbruster
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Proc Natl Acad Sci U S A 104:5163-8. 2007..Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo... - Screening the receptorome reveals molecular targets responsible for drug-induced side effects: focus on 'fen-phen'Vincent Setola
Case Western Reserve University School of Medicine, Department of Biochemistry, 2109 Adelbert Road, Cleveland, OH 44106, USA
Expert Opin Drug Metab Toxicol 1:377-87. 2005..Receptorome screening represents one of the most effective methods for identifying potentially serious drug-related side effects at the preclinical stage, thereby avoiding significant economic and human health consequences... - Ribosomal S6 kinase 2 directly phosphorylates the 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor, thereby modulating 5-HT2A signalingRyan T Strachan
Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
J Biol Chem 284:5557-73. 2009..To our knowledge, these findings are the first to demonstrate that a downstream member of the ERK/MAPK cascade phosphorylates a GPCR as well as mediates cross-talk between a growth factor and a GPCR... - Evidence for the preferential involvement of 5-HT2A serotonin receptors in stress- and drug-induced dopamine release in the rat medial prefrontal cortexElizabeth A Pehek
Department of Psychiatry, Case Western Reserve School of Medicine, Cleveland, OH 44106, USA
Neuropsychopharmacology 31:265-77. 2006..These findings may have implications for the pharmacological treatment of disorders resulting from or exacerbated by stress... - Molecular biology of serotonin receptors structure and function at the molecular levelWesley K Kroeze
Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
Curr Top Med Chem 2:507-28. 2002..Finally, examples will be given to demonstrate that a detailed knowledge of the predicted structure of one receptor can be useful for structure-based drug design... - Cell biology. A last GASP for GPCRs?John A Gray
Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106-4936, USA
Science 297:529-31. 2002 - A direct interaction of PSD-95 with 5-HT2A serotonin receptors regulates receptor trafficking and signal transductionZongqi Xia
Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA
J Biol Chem 278:21901-8. 2003..Taken together, the present work elucidates novel roles for PSD-95 in regulating the functional activity and intracellular trafficking of 5-HT2A receptors and possibly other GPCRs... - Why mice are neither miniature humans nor small rats: a cautionary tale involving 5-hydroxytryptamine-6 serotonin receptor species variantsVincent Setola
Department of Biochemistry, Psychiatry, and Neurosciences, Case Western University, 10900 Euclid Avenue, Room RT-500, Cleveland, OH 44106-4936, USA
Mol Pharmacol 64:1277-8. 2003 - L-homocysteine sulfinic acid and L-homocysteic acid stimulate phosphoinositide hydrolysis in rat cortical neuronsQi Shi
Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
Ann N Y Acad Sci 1003:461-3. 2003 - Mining the receptoromeBlaine N Armbruster
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
J Biol Chem 280:5129-32. 2005 - Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacologyMarilyn A Davies
Department of Biochemistry, Case Western Reserve University Medical School, 2109 Adelbert Road, Cleveland, OH 44106, USA
CNS Drug Rev 10:317-36. 2004..In the long-term studies, the use of aripiprazole was associated with continued efficacy, good compliance and increased time-to-relapse. Aripiprazole represents the first functionally selective atypical antipsychotic drug... - Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptorVincent Setola
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4935, USA
Mol Pharmacol 68:20-33. 2005..In conclusion, vdW interactions between residue 2.53 and the alpha-methyl group of SNF contribute to the ligand's 5-HT(2) receptor subtype-selective pharmacology... - Molecular targets for treating cognitive dysfunction in schizophreniaJohn A Gray
Department of Psychiatry, University of California, San Fransico, CA, USA
Schizophr Bull 33:1100-19. 2007.... - Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: receptor modeling studiesMałgorzata Dukat
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 0540, USA
J Med Chem 51:603-11. 2008..The results indicate that the presence or absence of an N1-benzenesulfonyl group is a major determinant of the manner in which tryptamine-related agents bind at 5-HT6 serotonin receptors... - Relating protein pharmacology by ligand chemistryMichael J Keiser
Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco California 94143 2550, USA
Nat Biotechnol 25:197-206. 2007..These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves... - Binding of methoxy-substituted N1-benzenesulfonylindole analogs at human 5-HT6 serotonin receptorsUma Siripurapu
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA
Bioorg Med Chem Lett 16:3793-6. 2006..Their 1,2,3,4-tetrahydrocarbazole counterparts behave differently... - Opportunities and challenges of psychiatric drug discovery: roles for scientists in academic, industry, and government settingsP Jeffrey Conn
Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232 6600, USA
Neuropsychopharmacology 33:2048-60. 2008..Also, increased attention should be focused on the development of early predictors of adverse effects of candidate compounds... - Ring substituted analogues of 5-aminomethyl-10,11-dihydro-dibenzo[a,d]cycloheptene (AMDH): potential modes of binding to the 5-HT(2A) receptorSrinivas Peddi
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA
Bioorg Med Chem Lett 13:2565-8. 2003..Comparison of the effects of substitution on affinities allowed assignment of potential binding modes in comparison with DOB-like agonists/antagonists and 3-substituted 1-(aminomethyl)-9,10-dihydroanthracene structures... - New insights into the function of M4 muscarinic acetylcholine receptors gained using a novel allosteric modulator and a DREADD (designer receptor exclusively activated by a designer drug)Vindhya Nawaratne
Drug Discovery Biology Laboratory, Monash Institute of Pharmaceutical Sciences, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
Mol Pharmacol 74:1119-31. 2008..These results provide conclusive evidence for the retention of a functional allosteric site on the M4 DREADD and highlight a role for residues Tyr113 and Ala203 in the transmission of cooperativity... - Engineering GPCR signaling pathways with RASSLsBruce R Conklin
Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, California 94158, USA
Nat Methods 5:673-8. 2008..Currently, RASSLs exist for the three major GPCR signaling pathways (G(s), G(i) and G(q)). We review these advances here to facilitate the use of these powerful and diverse tools... - Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivoAlan I Faden
Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Room EP 12, Washington, DC 20057, USA
J Cereb Blood Flow Metab 23:342-54. 2003..Thus, 35b shows none of the typical physiologic actions associated with TRH, but possesses neuroprotective actions in vivo and in vitro, and appears to attenuate both necrotic and apoptotic cell death... - Synthesis of potent and selective serotonin 5-HT1B receptor ligandsYiyun Huang
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
Bioorg Med Chem Lett 15:4786-9. 2005..Many of these new compounds displayed high affinity and selectivity for the 5-HT1B receptor and compound 6c was found to have the in vitro binding profile necessary for development as a PET radioligand... - In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRsVeronika Butterweck
Institute of Pharmacology and Toxicology, Westfälische Wilhelms Universität Muenster, Domagkstrasse 12, 48149 Muenster, Germany
Psychopharmacology (Berl) 162:193-202. 2002..Hypericum perforatum L. (St. John's wort; SJW) is one of the leading psychotherapeutic phytomedicines and great effort has been devoted to clarifying its mechanism of action... - Interaction of chiral MS-245 analogs at h5-HT6 receptorsCarmen Abate
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA
Bioorg Med Chem Lett 15:3510-3. 2005..Optically active pyrrolidinylmethylindole analogs related in structure to the benzenesulfonyltryptamine 5-HT(6) receptor antagonist MS-245 were evaluated and their R-isomers were found to bind with affinity higher than their S-enantiomers... - Geometry-affinity relationships of the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthraceneScott P Runyon
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, USA
J Med Chem 45:1656-64. 2002..Evaluation of conformationally constrained derivatives of AMDA suggests that a chain extended trans, gauche form is most likely responsible for high affinity... - Synthesis and in vitro pharmacology of novel heterocyclic muscarinic ligandsMarco De Amici
Istituto di Chimica Farmaceutica e Tossicologica, , Viale Abruzzi 42, Milan 20131, Italy
Farmaco 58:739-48. 2003..Quite similarly, chiral 3-oxo-Delta(2)-isoxazoline (+/-)-10 behaved as a weak antagonist unable to discriminate the different muscarinic receptor subtypes... - N-methylacetamide analog of salvinorin A: a highly potent and selective kappa-opioid receptor agonist with oral efficacyCecile Beguin
Department of Psychiatry, McLean Hospital, MRC 322A, 115 Mill Street, Belmont, MA 02478, USA
J Pharmacol Exp Ther 324:188-95. 2008.... - Novel oxotremorine-related heterocyclic derivatives: Synthesis and in vitro pharmacology at the muscarinic receptor subtypesClelia Dallanoce
Istituto di Chimica Farmaceutica e Tossicologica Pietro Pratesi, Universita degli Studi di Milano, Via Mangiagalli 25, Milano 20133, Italy
Bioorg Med Chem 15:7626-37. 2007.... - 1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligandsMase Lee
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA
Bioorg Med Chem Lett 15:1707-11. 2005..4-Sulfonyl analogs of 1-(1-naphthyl)piperazine bind at human 5-HT6 receptors and represent a novel class of human 5-HT6 receptor ligands... - Fluorinated diaryl sulfides as serotonin transporter ligands: synthesis, structure-activity relationship study, and in vivo evaluation of fluorine-18-labeled compounds as PET imaging agentsYiyun Huang
Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
J Med Chem 48:2559-70. 2005..Among these four ligands, three appear to be promising radioligands suitable for the labeling of SERT in vivo, with 18a providing a higher specific binding in vivo than 16 or 18b... - Functional selectivity and classical concepts of quantitative pharmacologyJonathan D Urban
Curriculum in Toxicology, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7160, USA
J Pharmacol Exp Ther 320:1-13. 2007..It also may be timely to revise classic concepts in quantitative pharmacology and relevant pharmacological conventions to incorporate these new concepts... - Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medicationsYasuyoshi Iso
Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
J Med Chem 49:1080-100. 2006..Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP... - The human polyomavirus, JCV, uses serotonin receptors to infect cellsGwendolyn F Elphick
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
Science 306:1380-3. 2004..A tagged 5HT2A receptor colocalized with labeled JCV in an endosomal compartment following internalization. Serotonin receptor antagonists may thus be useful in the treatment of progressive multifocal leukoencephalopathy... - Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptorsDonald Sikazwe
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0540, USA
J Med Chem 49:5217-25. 2006..A pharmacophore model is presented to account for some of the current findings... - Interaction of N1-unsubstituted and N1-benzenesulfonyltryptamines at h5-HT6 receptorsRenata Kolanos
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA
Bioorg Med Chem Lett 16:5832-5. 2006..201). Additionally, an examination of two rotationally constrained N1-benzenesulfonyltryptamine analogs indicates that a non-coplanar relationship between the two aryl groups might be preferred for interaction with the receptors... - The neurotensin agonist PD149163 increases Fos expression in the prefrontal cortex of the ratKimberly A Petrie
Department of Psychiatry, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN, USA
Neuropsychopharmacology 29:1878-88. 2004..Pretreatment with the high-affinity neurotensin antagonist, SR48692, blocked neurotensin agonist-induced Fos expression. These data suggest that neurotensin activates interneurons in the PFC of the rat... - Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targetsSivaraman Dandapani
Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA
J Org Chem 71:8934-45. 2006..Massively parallel screening of the complex DKPs against a panel of molecular targets identified novel ligands for a number of G-protein-coupled receptors (GPCRs)... - Molecular determinants in the second intracellular loop of the 5-hydroxytryptamine-1A receptor for G-protein couplingNeena Kushwaha
Ottawa Health Research Institute Neuroscience, and Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5
Mol Pharmacol 69:1518-26. 2006..Thus, the 5-HT1A receptor Ci2 domain determines Gbetagamma specificity and stabilizes Galphai-mediated signaling... - Binding of isotryptamines and indenes at h5-HT6 serotonin receptorsRenata Kolanos
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA
Bioorg Med Chem Lett 15:1987-91. 2005..The affinity of 3-benzyl-N(1)-(N,N-dimethylaminoethyl)indole (5, K(i)=32nM) and 1-benzyl-3-(N,N-dimethylaminoethyl)indene (11, K(i)=3nM) indicates that the indolic nitrogen atom is not essential for binding... - High-dose olanzapine for treatment-resistant schizophreniaBryan L Roth
Department of Pharmacology, Medicinal Chemistry and Psychiatry, University of North Carolina at Chapel Hill School of Medicine, NC 27599, USA
J Clin Psychiatry 69:176-7. 2008
Research Grants
- MOLECULAR MECHANISMS OF 5-HT RECEPTOR ACTIONSBryan Roth; Fiscal Year: 2005..A full molecular pharmacologic characterization of these compounds is essential prior to their use in humans. ..
- Structural Domains Essential for Serotonin Receptor PharmacologyBryan Roth; Fiscal Year: 2006..Novel techniques of protein biochemistry (hydroxyl-mediated 1H/2H exchange), cell biology (yeast 2-hybrid screening) and spectroscopy (FRET/BRET) will be used to arrive at testable models for 5-HT2A-Gq interactions. ..
- Targeting and Trafficking of 5-HT2A serotonin ReceptorsBryan Roth; Fiscal Year: 2006..Specific Aim 3: To determine whether the interaction between ribosomal S6-kinase-2 (RSK2) and 5-HT2A receptors has functional significance. ..
- Diterpines as Selective Kappa Opioid Receptor AgonistsBryan Roth; Fiscal Year: 2007..These studies are likely to clarify how Salvinorin A and related drugs of abuse mediate their actions at the molecular and cellular levels and will lead to treatments for the side-effects related to Salvinorin A abuse. ..
- Functional Selectivity: A Novel approach for CNS Drug DiscoveryBryan Roth; Fiscal Year: 2007..Understanding the relevance of functional selectivity of anti psychotics may provide novel targets with fewer side-effects, greater therapeutic selectivity, and enhanced efficacy for treating individuals with schizophrenia. ..