Bryan Roth

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. ncbi request reprint Progress towards better understanding and treatment of major psychiatric illnesses
    Atheir Abbas
    Case Western Reserve University, Department of Biochemistry, 2109 Adelbert Road, Cleveland, OH 44106, USA
    Drug Discov Today 10:960-2. 2005
  2. ncbi request reprint Molecular and cellular mechanisms for the polarized sorting of serotonin receptors: relevance for genesis and treatment of psychosis
    Bryan 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
  3. ncbi request reprint 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
  4. ncbi request reprint Screening the receptorome yields validated molecular targets for drug discovery
    Bryan 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
  5. ncbi request reprint Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders
    Bryan 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
  6. ncbi request reprint Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery
    Bryan 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
  7. ncbi request reprint Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia
    Bryan 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
  8. doi request reprint Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compound
    David N Wald
    Department of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106, USA
    Cancer Res 68:4369-76. 2008
  9. ncbi request reprint Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders
    Atheir Abbas
    Case Western Reserve University School of Medicine, Biochemistry, Cleveland, OH 44106, USA
    Expert Opin Pharmacother 9:3251-9. 2008
  10. ncbi request reprint Screening the receptorome: an efficient approach for drug discovery and target validation
    Ryan 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

Collaborators

Detail Information

Publications72

  1. ncbi request reprint Progress towards better understanding and treatment of major psychiatric illnesses
    Atheir Abbas
    Case Western Reserve University, Department of Biochemistry, 2109 Adelbert Road, Cleveland, OH 44106, USA
    Drug Discov Today 10:960-2. 2005
  2. ncbi request reprint Molecular and cellular mechanisms for the polarized sorting of serotonin receptors: relevance for genesis and treatment of psychosis
    Bryan 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...
  3. ncbi request reprint 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...
  4. ncbi request reprint Screening the receptorome yields validated molecular targets for drug discovery
    Bryan 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...
  5. ncbi request reprint Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders
    Bryan 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...
  6. ncbi request reprint Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery
    Bryan 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...
  7. ncbi request reprint Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia
    Bryan 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
  8. doi request reprint Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compound
    David 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...
  9. ncbi request reprint Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders
    Atheir 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...
  10. ncbi request reprint Screening the receptorome: an efficient approach for drug discovery and target validation
    Ryan 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...
  11. pmc PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptors
    Atheir 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...
  12. ncbi request reprint Screening the receptorome for plant-based psychoactive compounds
    Kerry Ann O'Connor
    Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106 4935, USA
    Life Sci 78:506-11. 2005
    ....
  13. ncbi request reprint Finding new tricks for old drugs: an efficient route for public-sector drug discovery
    KERRY A O'CONNOR
    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...
  14. ncbi request reprint Salvinorin A: from natural product to human therapeutics
    Timothy 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...
  15. ncbi request reprint H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs
    Wesley 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
    ....
  16. ncbi request reprint Screening the receptorome
    Wesley K Kroeze
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
    J Psychopharmacol 20:41-6. 2006
    ....
  17. pmc 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...
  18. ncbi request reprint 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
    ..Recent studies have suggested that the salutary actions of clozapine in schizophrenia may be due to selective activation of M(1) muscarinic receptors by clozapine and/or its major active metabolite N-desmethylclozapine...
  19. pmc Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo
    Atheir I Abbas
    Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
    Psychopharmacology (Berl) 205:119-28. 2009
    ....
  20. ncbi request reprint Receptorome screening for CNS drug discovery
    Timothy 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'...
  21. ncbi request reprint Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence affect plasma membrane targeting, ligand binding, and calcium influx in heterologous mammalian cells
    Phillip 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...
  22. ncbi request reprint 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro
    Vincent 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...
  23. ncbi request reprint Caveolin-1 interacts with 5-HT2A serotonin receptors and profoundly modulates the signaling of selected Galphaq-coupled protein receptors
    Anushree 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...
  24. ncbi request reprint The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT(2A) receptor induces agonist-independent internalization
    John 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...
  25. ncbi request reprint G-protein-coupled receptors at a glance
    Wesley 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
  26. ncbi request reprint Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization
    John 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...
  27. ncbi request reprint Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology
    David A Shapiro
    Department of Biochemistry, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, OH 44106 4935, USA
    Neuropsychopharmacology 28:1400-11. 2003
    ....
  28. ncbi request reprint 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 6
    David 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...
  29. pmc Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment
    Xi 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...
  30. pmc p90 Ribosomal S6 kinase 2, a novel GPCR kinase, is required for growth factor-mediated attenuation of GPCR signaling
    Ryan 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)...
  31. pmc p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling
    Douglas 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...
  32. pmc Arresting serotonin
    Atheir 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
  33. pmc Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand
    Blaine 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...
  34. ncbi request reprint 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...
  35. pmc Ribosomal S6 kinase 2 directly phosphorylates the 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor, thereby modulating 5-HT2A signaling
    Ryan 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...
  36. ncbi request reprint Evidence for the preferential involvement of 5-HT2A serotonin receptors in stress- and drug-induced dopamine release in the rat medial prefrontal cortex
    Elizabeth 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...
  37. ncbi request reprint Molecular biology of serotonin receptors structure and function at the molecular level
    Wesley 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...
  38. ncbi request reprint 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
  39. ncbi request reprint A direct interaction of PSD-95 with 5-HT2A serotonin receptors regulates receptor trafficking and signal transduction
    Zongqi 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...
  40. ncbi request reprint Why mice are neither miniature humans nor small rats: a cautionary tale involving 5-hydroxytryptamine-6 serotonin receptor species variants
    Vincent 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
  41. ncbi request reprint L-homocysteine sulfinic acid and L-homocysteic acid stimulate phosphoinositide hydrolysis in rat cortical neurons
    Qi Shi
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Ann N Y Acad Sci 1003:461-3. 2003
  42. ncbi request reprint Mining the receptorome
    Blaine N Armbruster
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    J Biol Chem 280:5129-32. 2005
  43. ncbi request reprint Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology
    Marilyn 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...
  44. ncbi request reprint Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor
    Vincent 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...
  45. pmc Molecular targets for treating cognitive dysfunction in schizophrenia
    John A Gray
    Department of Psychiatry, University of California, San Fransico, CA, USA
    Schizophr Bull 33:1100-19. 2007
    ....
  46. doi request reprint Binding of serotonin and N1-benzenesulfonyltryptamine-related analogs at human 5-HT6 serotonin receptors: receptor modeling studies
    Małgorzata 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...
  47. ncbi request reprint Relating protein pharmacology by ligand chemistry
    Michael 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...
  48. ncbi request reprint Binding of methoxy-substituted N1-benzenesulfonylindole analogs at human 5-HT6 serotonin receptors
    Uma 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...
  49. doi request reprint Opportunities and challenges of psychiatric drug discovery: roles for scientists in academic, industry, and government settings
    P 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...
  50. ncbi request reprint Ring substituted analogues of 5-aminomethyl-10,11-dihydro-dibenzo[a,d]cycloheptene (AMDH): potential modes of binding to the 5-HT(2A) receptor
    Srinivas 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...
  51. doi request reprint 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...
  52. pmc Engineering GPCR signaling pathways with RASSLs
    Bruce 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...
  53. ncbi request reprint Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivo
    Alan 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...
  54. ncbi request reprint Synthesis of potent and selective serotonin 5-HT1B receptor ligands
    Yiyun 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...
  55. ncbi request reprint In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRs
    Veronika 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...
  56. ncbi request reprint Interaction of chiral MS-245 analogs at h5-HT6 receptors
    Carmen 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...
  57. ncbi request reprint Geometry-affinity relationships of the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene
    Scott 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...
  58. ncbi request reprint Synthesis and in vitro pharmacology of novel heterocyclic muscarinic ligands
    Marco De Amici
    Istituto di Chimica Farmaceutica e Tossicologica, Universita di Milano, 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...
  59. ncbi request reprint N-methylacetamide analog of salvinorin A: a highly potent and selective kappa-opioid receptor agonist with oral efficacy
    Cecile Beguin
    Department of Psychiatry, McLean Hospital, MRC 322A, 115 Mill Street, Belmont, MA 02478, USA
    J Pharmacol Exp Ther 324:188-95. 2008
    ....
  60. ncbi request reprint Novel oxotremorine-related heterocyclic derivatives: Synthesis and in vitro pharmacology at the muscarinic receptor subtypes
    Clelia 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
    ....
  61. ncbi request reprint 1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligands
    Mase 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...
  62. ncbi request reprint Fluorinated diaryl sulfides as serotonin transporter ligands: synthesis, structure-activity relationship study, and in vivo evaluation of fluorine-18-labeled compounds as PET imaging agents
    Yiyun 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...
  63. ncbi request reprint Functional selectivity and classical concepts of quantitative pharmacology
    Jonathan 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...
  64. ncbi request reprint 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 medications
    Yasuyoshi 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...
  65. ncbi request reprint The human polyomavirus, JCV, uses serotonin receptors to infect cells
    Gwendolyn 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...
  66. ncbi request reprint Binding of sulfonyl-containing arylalkylamines at human 5-HT6 serotonin receptors
    Donald 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...
  67. ncbi request reprint Interaction of N1-unsubstituted and N1-benzenesulfonyltryptamines at h5-HT6 receptors
    Renata 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...
  68. ncbi request reprint The neurotensin agonist PD149163 increases Fos expression in the prefrontal cortex of the rat
    Kimberly 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...
  69. ncbi request reprint Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets
    Sivaraman 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)...
  70. ncbi request reprint Molecular determinants in the second intracellular loop of the 5-hydroxytryptamine-1A receptor for G-protein coupling
    Neena 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...
  71. ncbi request reprint Binding of isotryptamines and indenes at h5-HT6 serotonin receptors
    Renata 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...
  72. ncbi request reprint High-dose olanzapine for treatment-resistant schizophrenia
    Bryan 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 Grants5

  1. MOLECULAR MECHANISMS OF 5-HT RECEPTOR ACTIONS
    Bryan Roth; Fiscal Year: 2005
    ..A full molecular pharmacologic characterization of these compounds is essential prior to their use in humans. ..
  2. Structural Domains Essential for Serotonin Receptor Pharmacology
    Bryan 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. ..
  3. Targeting and Trafficking of 5-HT2A serotonin Receptors
    Bryan 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. ..
  4. Diterpines as Selective Kappa Opioid Receptor Agonists
    Bryan 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. ..
  5. Functional Selectivity: A Novel approach for CNS Drug Discovery
    Bryan 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. ..