B L Roth

Summary

Affiliation: Case Western Reserve University
Country: USA

Publications

  1. ncbi request reprint Insights into the structure and function of 5-HT(2) family serotonin receptors reveal novel strategies for therapeutic target development
    Bryan L Roth
    Departments of Biochemistry, Neurosciences and Psychiatry, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, Ohio, 44106 4935, USA
    Expert Opin Ther Targets 5:685-695. 2001
  2. pmc Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist
    Bryan L Roth
    National Institute of Mental Health Psychoactive Drug Screening Program and Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 99:11934-9. 2002
  3. ncbi request reprint Identification of conserved aromatic residues essential for agonist binding and second messenger production at 5-hydroxytryptamine2A receptors
    B L Roth
    Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, Ohio 44106 4935, USA
    Mol Pharmacol 52:259-66. 1997
  4. ncbi request reprint The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor
    B L Roth
    Department of Biochemistry, Rm W438, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, OH 44106 4935, USA
    Psychopharmacology (Berl) 157:111-4. 2001
  5. ncbi request reprint High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model
    B L Roth
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4935, USA
    J Pharmacol Exp Ther 280:576-83. 1997
  6. ncbi request reprint The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis
    A Bhatnagar
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
    J Biol Chem 276:8269-77. 2001
  7. ncbi request reprint Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor
    L Rauser
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106-4935, USA
    J Pharmacol Exp Ther 299:83-9. 2001
  8. 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
  9. ncbi request reprint Synthesis of potent and selective dopamine D(4) antagonists as candidate radioligands
    Y Huang
    Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Bioorg Med Chem Lett 11:1375-7. 2001
  10. ncbi request reprint Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies
    M A Davies
    Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, OH 44106 4935, USA
    Pharmacogenomics J 6:42-51. 2006

Collaborators

Detail Information

Publications92

  1. ncbi request reprint Insights into the structure and function of 5-HT(2) family serotonin receptors reveal novel strategies for therapeutic target development
    Bryan L Roth
    Departments of Biochemistry, Neurosciences and Psychiatry, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, Ohio, 44106 4935, USA
    Expert Opin Ther Targets 5:685-695. 2001
    ..Thus, provided appropriately sophisticated drug design strategies are employed, it is likely that uniquely valuable medications will result which could have great potential for treating a variety of mental and physical illnesses...
  2. pmc Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist
    Bryan L Roth
    National Institute of Mental Health Psychoactive Drug Screening Program and Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 99:11934-9. 2002
    ..g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception...
  3. ncbi request reprint Identification of conserved aromatic residues essential for agonist binding and second messenger production at 5-hydroxytryptamine2A receptors
    B L Roth
    Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, Ohio 44106 4935, USA
    Mol Pharmacol 52:259-66. 1997
    ..These results demonstrate that highly conserved aromatic residues residing in neighboring helices provide the optimum environment for both agonist binding and activation of 5-HT2A receptors...
  4. ncbi request reprint The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor
    B L Roth
    Department of Biochemistry, Rm W438, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, OH 44106 4935, USA
    Psychopharmacology (Berl) 157:111-4. 2001
    ..s-Fluorocarazolol [(S)-FCZ] is the major positron emission tomography (PET) ligand currently used to visualize central beta-adrenergic receptors in vivo, although its pharmacology is incompletely known...
  5. ncbi request reprint High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model
    B L Roth
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4935, USA
    J Pharmacol Exp Ther 280:576-83. 1997
    ..These results are consistent with recent models of G protein-receptor functioning (e.g., modified ternary complex model) that predict that additional transition states of the receptor-ligand complex are essential for agonist efficacy...
  6. ncbi request reprint The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis
    A Bhatnagar
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
    J Biol Chem 276:8269-77. 2001
    ....
  7. ncbi request reprint Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor
    L Rauser
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106-4935, USA
    J Pharmacol Exp Ther 299:83-9. 2001
    ....
  8. 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...
  9. ncbi request reprint Synthesis of potent and selective dopamine D(4) antagonists as candidate radioligands
    Y Huang
    Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Bioorg Med Chem Lett 11:1375-7. 2001
    ..All new compounds display high affinity and selectivity for the D(4) receptors and compounds 5b, 5d, and 5e were identified as candidates for radioligand development...
  10. ncbi request reprint Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies
    M A Davies
    Department of Psychiatry, Case Western Reserve University Medical School, Cleveland, OH 44106 4935, USA
    Pharmacogenomics J 6:42-51. 2006
    ..In all, our results show that the in vitro pharmacological effects of the SNPs are drug specific...
  11. ncbi request reprint Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists
    J A Gray
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4935, USA
    Brain Res Bull 56:441-51. 2001
    ..Finally, a review of the cellular and molecular mechanisms that may be responsible for agonist-mediated desensitization and internalization of 5-HT(2A) receptors will be presented...
  12. ncbi request reprint Cell-type specific effects of endocytosis inhibitors on 5-hydroxytryptamine(2A) receptor desensitization and resensitization reveal an arrestin-, GRK2-, and GRK5-independent mode of regulation in human embryonic kidney 293 cells
    J A Gray
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4935, USA
    Mol Pharmacol 60:1020-30. 2001
    ..Additionally, these results imply that novel GRK and arrestin-independent mechanisms of 5-HT(2A) receptor desensitization and resensitization exist in HEK-293 cells...
  13. 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...
  14. 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...
  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 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
  17. ncbi request reprint Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations
    Charles Chavkin
    Department of Biochemistry, University of Washington School of Medicine, Seattle, Washington, USA
    J Pharmacol Exp Ther 308:1197-203. 2004
    ..Salvinorin A thus represents the first known naturally occurring non-nitrogenous full agonist at kappa-opioid receptors...
  18. 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...
  19. ncbi request reprint L-homocysteine sulfinic acid and other acidic homocysteine derivatives are potent and selective metabotropic glutamate receptor agonists
    Qi Shi
    Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Pharmacol Exp Ther 305:131-42. 2003
    ..The relevance of these findings for the role of mGluRs in the pathogenesis of homocysteine-mediated phenomena is discussed...
  20. ncbi request reprint Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors
    Feng Yan
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA
    Biochemistry 44:8643-51. 2005
    ..When these findings are taken together, they imply that the diterpenoid salvinorin A utilizes unique residues within a commonly shared binding pocket to selectively activate KORs...
  21. 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...
  22. 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
    ....
  23. ncbi request reprint Differential helical orientations among related G protein-coupled receptors provide a novel mechanism for selectivity. Studies with salvinorin A and the kappa-opioid receptor
    Timothy A Vortherms
    Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 282:3146-56. 2007
    ..These findings imply that differences in the helical orientation of helix 2 are critical for the selectivity of salvinorin A binding to KOR and provide a structurally novel basis for ligand selectivity...
  24. ncbi request reprint D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs
    B L Roth
    Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH 44106 4935, USA
    Psychopharmacology (Berl) 120:365-8. 1995
    ..Thus, D4 dopamine receptor affinity, used as a single measure, does not distinguish between the group of typical and atypical antipsychotic drugs analyzed...
  25. ncbi request reprint Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors
    B L Roth
    Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio
    J Pharmacol Exp Ther 268:1403-10. 1994
    ..Several dopamine-selective antipsychotic agents (raclopride, rimcazole and penfluridol) had essentially no affinity for either the 5-HT6 or 5-HT7 receptors (Ki values > 5000 nM).(ABSTRACT TRUNCATED AT 250 WORDS)..
  26. ncbi request reprint IRAS splice variants
    J E Piletz
    Department of Psychiatry, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA
    Ann N Y Acad Sci 1009:419-26. 2003
    ..Subtype-selective cDNA expression constructs were therefore generated and used to transfect CHO cells. High-affinity I(1) binding was endowed by IRAS-M and IRAS-L, but not by IRAS-S transfection...
  27. ncbi request reprint Distribution of serotonin 5-HT(2A) receptors in afferents of the rat striatum
    M Bubser
    Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA
    Synapse 39:297-304. 2001
    ....
  28. ncbi request reprint The pipeline and future of drug development in schizophrenia
    J A Gray
    Department of Psychiatry, University of California, San Francisco, CA 94143 0984, USA
    Mol Psychiatry 12:904-22. 2007
    ..Thus, this is an exciting and pivotal time for the development of truly novel approaches to drug development and treatment of complex disorders like schizophrenia...
  29. 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...
  30. 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
    ....
  31. 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...
  32. pmc Serotonin-2C and -2a receptor co-expression on cells in the rat medial prefrontal cortex
    C Nocjar
    Louis Stokes Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA Department of Psychiatry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA Electronic address
    Neuroscience 297:22-37. 2015
    ..Thus a complex interplay of cortical 5-HT2A and 5-HT2C receptor mechanisms exists, which if altered, could modulate efferent brain systems implicated in mental illness. ..
  33. ncbi request reprint The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro
    Z Xia
    Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
    Neuroscience 122:907-20. 2003
    ....
  34. 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...
  35. 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...
  36. 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
    ....
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. ncbi request reprint Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group
    C Nocjar
    Louis Stokes Cleveland VA Medical Center 151 W, OH 44106, USA
    Neuroscience 111:163-76. 2002
    ..Thus, findings in this study could have important implications for understanding 5-HT and dopamine circuitry dysfunction in schizophrenia...
  44. pmc Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats
    Christina L Nemeth
    Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
    Psychopharmacology (Berl) 210:263-74. 2010
    ..One way to study these states in rodents is with tests that require attention and visual perception for correct performance...
  45. 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
    ....
  46. 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
    ....
  47. 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...
  48. 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...
  49. 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...
  50. 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'...
  51. 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...
  52. 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
    ....
  53. 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...
  54. doi request reprint Galpha-subunits differentially alter the conformation and agonist affinity of kappa-opioid receptors
    Feng Yan
    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
    Biochemistry 47:1567-78. 2008
    ..These data are significant because they demonstrate that Galpha-subunits differentially modulate the conformation and agonist affinity of a prototypical GPCR...
  55. 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)...
  56. 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
  57. 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...
  58. ncbi request reprint Salvinorin A: the "magic mint" hallucinogen finds a molecular target in the kappa opioid receptor
    Douglas J Sheffler
    Department of Biochemistry, Case Western Reserve University Medical School, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    Trends Pharmacol Sci 24:107-9. 2003
    ....
  59. pmc Genetic deletion of p90 ribosomal S6 kinase 2 alters patterns of 5-hydroxytryptamine 2A serotonin receptor functional selectivity
    Ryan T Strachan
    Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, Ohio, USA
    Mol Pharmacol 77:327-38. 2010
    ..This study provides the first evidence that deletion of a single kinase can elicit profound changes in patterns of agonist functional selectivity...
  60. 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...
  61. ncbi request reprint Salvinorin A: a novel and highly selective kappa-opioid receptor agonist
    Feng Yan
    Department of Biochemistry, RM W441, Case Western Reserve University Medical School, 2109 Adelbert Road, Cleveland, OH 44106, USA
    Life Sci 75:2615-9. 2004
    ..Because salvinorin A profoundly alters human consciousness and perception, a study of how salvinorin A exerts its actions on KORs may yield novel insights into the molecular and cellular basis of uniquely human higher cortical functions...
  62. 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
  63. 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...
  64. ncbi request reprint Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice
    Michael A Ansonoff
    Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School UMDNJ RWJMS, 675 Hoes Lane, Piscataway, NJ 08854, USA
    J Pharmacol Exp Ther 318:641-8. 2006
    ..divinorum, selective for kappa(1)-opioid receptors, and that salvinorin A and specific structurally related analogs produce behavioral effects that require the kappa-opioid receptor...
  65. ncbi request reprint Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1
    Matthew S Goldberg
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
    Neuron 45:489-96. 2005
    ..Furthermore, DJ-1(-/-) mice displayed hypoactivity in the open field. Collectively, our findings suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor-mediated functions...
  66. 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
    ....
  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 Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons
    Matthew S Goldberg
    Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Biol Chem 278:43628-35. 2003
    ..Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice...
  69. 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...
  70. 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...
  71. 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...
  72. 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...
  73. 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...
  74. 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...
  75. 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...
  76. 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...
  77. pmc Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist
    Thomas A Munro
    School of Chemistry, The University of Melbourne, Victoria, 3010, Australia
    J Med Chem 48:345-8. 2005
    ..Other salvinorins showed negligible binding affinity at the KOR. None of the compounds bound to mu or delta opioid receptors...
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. ncbi request reprint Spiro[9,10-dihydroanthracene]-9,3'-pyrrolidine-a structurally unique tetracyclic 5-HT2A receptor antagonist
    Srinivas Peddi
    Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298 0540, USA
    Eur J Pharmacol 482:335-7. 2003
    ..Thus, SpAMDA may be a structurally novel parent of a new class of 5-HT(2A) receptor antagonists that binds to the receptor in a unique fashion that is distinct from the binding topology of existing 5-HT(2A) receptor antagonists...
  83. 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...
  84. ncbi request reprint Bioisosteric modification of salvinorin A, a potent and selective kappa-opioid receptor agonist
    D Jeremy Stewart
    Department of Pharmacognosy and National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677 1848, USA
    Arzneimittelforschung 56:269-75. 2006
    ..Intermediates, which lack a beta-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR...
  85. 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...
  86. 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...
  87. ncbi request reprint WAY-100635 is a potent dopamine D4 receptor agonist
    Benjamin R Chemel
    Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907 2091, USA
    Psychopharmacology (Berl) 188:244-51. 2006
    ..Results from our studies suggested that WAY-100635 was potently inducing effects unrelated to its 5-HT1A receptor affinity. In the present work, we evaluated the in vitro pharmacology of this compound at two D2-like receptor subtypes...
  88. ncbi request reprint In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates
    Richard B Rothman
    Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA
    J Pharmacol Exp Ther 307:138-45. 2003
    ....
  89. 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)...
  90. 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...
  91. pmc Convenient synthesis and in vitro pharmacological activity of 2-thioanalogs of salvinorins A and B
    Ruslan V Bikbulatov
    Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677 1848, USA
    Bioorg Med Chem Lett 17:2229-32. 2007
    ..Obtained compounds were examined for receptor binding affinity. Analogs with the same configuration at carbon atom C-2 as in natural salvinorin A showed higher affinity to KOR than their corresponding epimers...
  92. 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...