Bryan Roth

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. 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
  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 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
  4. 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
  5. 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
  6. pmc Irving Page Lecture: 5-HT(2A) serotonin receptor biology: interacting proteins, kinases and paradoxical regulation
    Bryan L Roth
    Department of Pharmacology, Program in Neurosciences, Lineberger Cancer Center, NIMH Psychoactive Drug Screening Program, and Division of Medicinal Chemistry and Natural Products, Room 4072, Genetic Medicine Building, University of North Carolina Chapel Hill Medical School, Chapel Hill, NC 27514, USA
    Neuropharmacology 61:348-54. 2011
  7. 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
  8. 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
  9. 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
  10. 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

Collaborators

  • H Y Meltzer
  • S G Grant
  • P Conn
  • Seth Y Ablordeppey
  • John J Irwin
  • Wesley K Kroeze
  • Atheir I Abbas
  • Niels H Jensen
  • Blaine N Armbruster
  • Sarah C Rogan
  • Prem N Yadav
  • Shuyun Dong
  • Marilyn A Davies
  • Paul Ernsberger
  • Ying Pei
  • Marc G Caron
  • Atheir Abbas
  • Vindhya Nawaratne
  • John A Gray
  • Michael J Keiser
  • Ryan T Strachan
  • Timothy A Vortherms
  • KERRY A O'CONNOR
  • Sandra J Hufeisen
  • Kimberly A Petrie
  • Douglas J Sheffler
  • David A Shapiro
  • Marco De Amici
  • Martilias S Farrell
  • Margaret I Arbuckle
  • Peter B Hedlund
  • Thuy B Tran
  • Xi Ping Huang
  • Wei Dong Yao
  • Ramona M Rodriguiz
  • William C Wetsel
  • Arthur Christopoulos
  • Katie Leach
  • Nur Suratman
  • Richard E Loiacono
  • Richard B Rothman
  • Christian C Felder
  • Patrick M Sexton
  • Stefan Herlitze
  • Brian K Shoichet
  • Mark H Pausch
  • Xiang Li
  • Gina Ferrara
  • Beth Ann Compton-Toth
  • Michael Bubser
  • M Duff Davis
  • Ariel Y Deutch
  • Cheryl D Casey
  • David R Sibley
  • Richard Mailman
  • Carlo De Micheli
  • Karu Jayathilake
  • Elisabetta Barocelli
  • Vigilio Ballabeni
  • Paola Conti
  • Beth A Popadak
  • Ezio Fasoli
  • Sean Renock
  • Sean M Renock
  • Simona Bertoni
  • Louis A Chiodo
  • SeAnna Steinberg
  • Elaine Arrington
  • Li Xin Liu
  • Mariannina Impicciatore

Detail Information

Publications35

  1. 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
    ....
  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 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
    ....
  4. 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...
  5. 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...
  6. pmc Irving Page Lecture: 5-HT(2A) serotonin receptor biology: interacting proteins, kinases and paradoxical regulation
    Bryan L Roth
    Department of Pharmacology, Program in Neurosciences, Lineberger Cancer Center, NIMH Psychoactive Drug Screening Program, and Division of Medicinal Chemistry and Natural Products, Room 4072, Genetic Medicine Building, University of North Carolina Chapel Hill Medical School, Chapel Hill, NC 27514, USA
    Neuropharmacology 61:348-54. 2011
    ..I highlight the role of serotonin receptor interacting proteins and the emerging paradigm of G-protein coupled receptor functional selectivity...
  7. 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
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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
  13. 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...
  14. pmc Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo
    Prem N Yadav
    Department of Pharmacology, University of North Carolina, Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
    J Pharmacol Exp Ther 339:99-105. 2011
    ..The significance of these findings with respect to atypical antipsychotic drug action is discussed...
  15. pmc Remote control of neuronal signaling
    Sarah C Rogan
    University of North Carolina School of Medicine, Department of Pharmacology, 120 Mason Farm Rd, Chapel Hill, NC 27514, USA
    Pharmacol Rev 63:291-315. 2011
    ..Although none of these tools is perfect, each has advantages and disadvantages, which we describe, and they are all still works in progress. We conclude with suggestions for improving upon the existing tools...
  16. 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...
  17. 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
  18. ncbi request reprint Massively parallel screening of the receptorome
    Niels H Jensen
    Department of Pharmacology School of Medicine and Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina Chapel Hill Medical School, Chapel Hill, NC 27599, USA
    Comb Chem High Throughput Screen 11:420-6. 2008
    ..A third, relatively new area is the identification of inert compounds as agonists for engineered designer receptors that no longer respond to their natural ligand (DREADDs) but exhibit unchanged signaling properties...
  19. 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...
  20. 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
    ....
  21. 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...
  22. doi request reprint Generation of designer receptors exclusively activated by designer drugs (DREADDs) using directed molecular evolution
    Ying Pei
    University of North Carolina, Chapel Hill, North Carolina, USA
    Curr Protoc Neurosci . 2010
    ..These methods are general and suitable for any GPCRs that can be functionally expressed in yeast...
  23. doi request reprint Directed molecular evolution of DREADDs: a generic approach to creating next-generation RASSLs
    Shuyun Dong
    Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
    Nat Protoc 5:561-73. 2010
    ..This protocol should help improve the experimental targeting of select cell populations...
  24. 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
    ....
  25. ncbi request reprint N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity
    Niels H Jensen
    Department of Pharmacology, University of North Carolina Medical School, Chapel Hill, NC 27599, USA
    Neuropsychopharmacology 33:2303-12. 2008
    ..Possible contributions of this metabolite to the side effects of quetiapine are discussed...
  26. 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...
  27. 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...
  28. 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...
  29. 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...
  30. 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
    ....
  31. 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...
  32. 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...
  33. pmc Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one
    Seth Y Ablordeppey
    Division of Basic Pharmaceutical Sciences, Florida A and M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA
    Bioorg Med Chem 16:7291-301. 2008
    ..In in vivo mouse and rat models to evaluate its efficacy and propensity to elicit catalepsy and hence EPS in humans, compound 13 showed similar efficacy as clozapine and did not produce catalepsy at five times its ED(50) value...
  34. 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...
  35. ncbi request reprint Evaluation of the eutomer of 4-{3-(4-chlorophenyl)-3-hydroxypyrrolidin-1-yl}-1-(4-fluorophenyl)butan-1-one, {(+)-SYA 09}, a pyrrolidine analog of haloperidol
    Seth Y Ablordeppey
    Division of Basic Pharmaceutical Sciences, Florida A and M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA
    Bioorg Med Chem Lett 16:3219-23. 2006
    ..2 (D2Ki/D4Ki ratio = 14.2). In an animal model of antipsychotic efficacy, the (+)-SYA 09 was efficacious with an ED50 value of 1.6 mg/kg, i.p., and at twice this value, (+)-SYA 09 did not induce significant catalepsy in rats...

Research Grants26

  1. Diterpines as Selective Kappa Opioid Receptor Agonists
    Bryan Roth; Fiscal Year: 2006
    ..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. ..
  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: 2009
    ..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 L Roth; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Salvia divinorum and its active ingredient salvinorin A represent emerging drugs of abuse in the US. These studies could lead to novel treatments for drug abuse. ..
  5. STRUCTURAL DOMAINS FOR SEROTONIN RECEPTOR PHARMACOLOGY
    Bryan Roth; Fiscal Year: 2000
    ..These findings will be useful for the design and synthesis of new medications to treat psychiatric diseases. ..
  6. REGULATION OF 5HT2A RECEPTOR TRAFFICKING
    Bryan Roth; Fiscal Year: 2003
    ..Finally, novel insights into the mechanism by which receptors are regulated at the cellular and molecular levels will be obtained with the proposed studies. ..
  7. Targeting and Trafficking of 5-HT2A serotonin Receptors
    Bryan L Roth; Fiscal Year: 2010
    ..This knowledge will help to clarify the mechanism by which these medications are effective in alleviating human illness. ..