S Kapur

Summary

Affiliation: Centre for Addiction and Mental Health
Country: Canada

Publications

  1. pmc How antipsychotics work-from receptors to reality
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada M5S 1A1 University of Toronto, Toronto, Canada
    NeuroRx 3:10-21. 2006
  2. ncbi request reprint Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia
    S Kapur
    Schizophrenia Program, PET Centre, CAMH, Toronto, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8
    Annu Rev Med 52:503-17. 2001
  3. ncbi request reprint Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine
    S Kapur
    PET Centre, Clarke Division, CAMH, Toronto, ONT Canada
    Am J Psychiatry 158:311-4. 2001
  4. ncbi request reprint Dopamine D(2) receptor blockade by haloperidol. (3)H-raclopride reveals much higher occupancy than EEDQ
    S Kapur
    Schizophrenia Program, CAMH, Ontario, Toronto, Canada
    Neuropsychopharmacology 23:595-8. 2000
  5. ncbi request reprint Drug-induced receptor occupancy: substantial differences in measurements made in vivo vs ex vivo
    S Kapur
    Schizophrenia Program and PET Centre, The Clarke Division of the CAMH, Toronto, Ontario, Canada
    Psychopharmacology (Berl) 157:168-71. 2001
  6. pmc Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action
    S Kapur
    Department of Psychiatry, University of Toronto, Ont
    J Psychiatry Neurosci 25:161-6. 2000
  7. ncbi request reprint Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: a suggested solution based on in vivo occupancy
    Shitij Kapur
    Centre for Addiction and Mental Health, Clarke Site 250 College Street Toronto, Ontario Canada M5R 1T8
    J Pharmacol Exp Ther 305:625-31. 2003
  8. ncbi request reprint The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats
    S Kapur
    Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5R 1T8
    J Pharmacol Exp Ther 302:1129-34. 2002
  9. ncbi request reprint Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis
    S Kapur
    Schizophrenia Program and the PET Centre of the Centre for Addiction and Mental Health, University of Toronto, Canada
    Am J Psychiatry 158:360-9. 2001
  10. ncbi request reprint Half a century of antipsychotics and still a central role for dopamine D2 receptors
    Shitij Kapur
    Schizophrenia Program, CAMH, Toronto, ON, Canada
    Prog Neuropsychopharmacol Biol Psychiatry 27:1081-90. 2003

Detail Information

Publications102 found, 100 shown here

  1. pmc How antipsychotics work-from receptors to reality
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada M5S 1A1 University of Toronto, Toronto, Canada
    NeuroRx 3:10-21. 2006
    ..The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed...
  2. ncbi request reprint Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia
    S Kapur
    Schizophrenia Program, PET Centre, CAMH, Toronto, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5T 1R8
    Annu Rev Med 52:503-17. 2001
    ..e. positive, negative, cognitive, and affective) with more selective drugs that can be combined and individually titrated to the needs of each patient...
  3. ncbi request reprint Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine
    S Kapur
    PET Centre, Clarke Division, CAMH, Toronto, ONT Canada
    Am J Psychiatry 158:311-4. 2001
    ....
  4. ncbi request reprint Dopamine D(2) receptor blockade by haloperidol. (3)H-raclopride reveals much higher occupancy than EEDQ
    S Kapur
    Schizophrenia Program, CAMH, Ontario, Toronto, Canada
    Neuropsychopharmacology 23:595-8. 2000
    ....
  5. ncbi request reprint Drug-induced receptor occupancy: substantial differences in measurements made in vivo vs ex vivo
    S Kapur
    Schizophrenia Program and PET Centre, The Clarke Division of the CAMH, Toronto, Ontario, Canada
    Psychopharmacology (Berl) 157:168-71. 2001
    ..While these methods are often used interchangeably, there has been no systematic comparison of their sensitivities and consistency...
  6. pmc Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action
    S Kapur
    Department of Psychiatry, University of Toronto, Ont
    J Psychiatry Neurosci 25:161-6. 2000
    ..The objective of this study was to determine the relationship between kon, koff and the affinity (Ki) of antipsychotic agents for the D2 receptors, with particular reference to typical and atypical antipsychotic agents...
  7. ncbi request reprint Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: a suggested solution based on in vivo occupancy
    Shitij Kapur
    Centre for Addiction and Mental Health, Clarke Site 250 College Street Toronto, Ontario Canada M5R 1T8
    J Pharmacol Exp Ther 305:625-31. 2003
    ..The study provides a rationale as well as clinically comparable dosing regimens for animal studies and raises questions about the inferences drawn from previous studies that have used doses unrepresentative of the clinical situation...
  8. ncbi request reprint The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats
    S Kapur
    Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5R 1T8
    J Pharmacol Exp Ther 302:1129-34. 2002
    ..1 = 6), olanzapine (0.30/0.43 = 0.7). These results indicate that dissociation between central and peripheral D2 receptor occupancy is a major determinant of the degree of prolactin elevation observed at therapeutic doses...
  9. ncbi request reprint Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis
    S Kapur
    Schizophrenia Program and the PET Centre of the Centre for Addiction and Mental Health, University of Toronto, Canada
    Am J Psychiatry 158:360-9. 2001
    ..This article provides a new hypothesis about the mechanism of action of atypical antipsychotics...
  10. ncbi request reprint Half a century of antipsychotics and still a central role for dopamine D2 receptors
    Shitij Kapur
    Schizophrenia Program, CAMH, Toronto, ON, Canada
    Prog Neuropsychopharmacol Biol Psychiatry 27:1081-90. 2003
    ..g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology...
  11. ncbi request reprint Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia
    Shitij Kapur
    Clarke Division of the Centre for Addiction and Mental Health, 250 College St, Toronto, Ont M5T 1R8, Canada
    Am J Psychiatry 160:13-23. 2003
    ..The objective of this overview is to link the neurobiology (brain), the phenomenological experience (mind), and pharmacological aspects of psychosis-in-schizophrenia into a unitary framework...
  12. ncbi request reprint NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia
    S Kapur
    Center for Addiction and Mental Health, Clarke Site, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5R 1T8
    Mol Psychiatry 7:837-44. 2002
    ..These findings confound the inferences one can draw from the ketamine/PCP models of schizophrenia...
  13. ncbi request reprint 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation
    S Kapur
    Schizophrenia Division, Clarke Institute of Psychiatry, Toronto, Ont, Canada
    Am J Psychiatry 155:921-8. 1998
    ..The purpose of this study was to investigate olanzapine's binding to the serotonin 5-HT2 and dopamine D2 receptors in schizophrenic patients being treated with clinically relevant doses...
  14. ncbi request reprint Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia
    S Kapur
    The Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, ON, Canada
    Am J Psychiatry 156:286-93. 1999
    ..The purpose of this study was to compare the D2 and serotonin 5-HT2 receptor occupancies of these drugs in patients receiving multiple-dose, steady-state regimens...
  15. ncbi request reprint PET evidence that loxapine is an equipotent blocker of 5-HT2 and D2 receptors: implications for the therapeutics of schizophrenia
    S Kapur
    Schizophrenia Division, Clarke Institute of Psychiatry, University of Toronto, Canada
    Am J Psychiatry 154:1525-9. 1997
    ..The purpose of this study was to document loxapine's 5-HT2 and D2 receptor occupancy in vivo in patients with psychoses...
  16. ncbi request reprint The D2 receptor occupancy profile of loxapine determined using PET
    S Kapur
    Schizophrenia Division, Clarke Institute of Psychiatry, Toronto, ON, Canada
    Neuropsychopharmacology 15:562-6. 1996
    ..This dose range is much lower than that used in most clinical settings and points to the potential efficacy of loxapine at lower doses...
  17. ncbi request reprint A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy
    S Kapur
    Department of Psychiatry, University of Toronto, Ontario
    Arch Gen Psychiatry 57:553-9. 2000
    ..The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile...
  18. ncbi request reprint A voxel-by-voxel analysis of [18F]setoperone PET data shows no substantial serotonin 5-HT(2A) receptor changes in schizophrenia
    N P Verhoeff
    PET Centre and Schizophrenia and Continuing Care Division, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, ON, M5T 1R8, Toronto, Canada
    Psychiatry Res 99:123-35. 2000
    ..Thus, in agreement with the previous ROI studies, voxel-by-voxel analysis confirmed the lack of substantial 5-HT(2A)R BP differences between schizophrenic patients and control subjects...
  19. ncbi request reprint High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET study
    S Kapur
    PET Centre, Clarke Institute of Psychiatry, Toronto, Ont, Canada
    Am J Psychiatry 153:948-50. 1996
    ..The purpose of this study was to determine the dopamine D2 receptor occupancy induced by low-dose haloperidol treatment in a prospective trial...
  20. ncbi request reprint A new framework for investigating antipsychotic action in humans: lessons from PET imaging
    S Kapur
    Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, ON, Canada
    Mol Psychiatry 3:135-40. 1998
    ..The justification, limitations and the value of this framework in understanding and investigating newer antipsychotics is discussed...
  21. ncbi request reprint D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PET
    G Remington
    Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ontario, Canada
    J Clin Psychiatry 60:15-9. 1999
    ..Combined serotonin-2/dopamine-2 (5-HT2/D2) antagonism represents one such model, and we now have PET evidence available that can be extrapolated to our understanding and clinical use of both conventional and novel antipsychotics...
  22. ncbi request reprint A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects
    N P Verhoeff
    PET Centre and Schizophrenia and Continuing Care Division, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    Neuropsychopharmacology 25:213-23. 2001
    ....
  23. ncbi request reprint Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging study
    J H Meyer
    Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, Ont, Canada
    Am J Psychiatry 156:1029-34. 1999
    ..The objective of this study was to evaluate 5-HT2 receptors in depressed patients who were medication-free and who had not made recent suicide attempts...
  24. ncbi request reprint Significant dissociation of brain and plasma kinetics with antipsychotics
    Johannes Tauscher
    Schizophrenia PET program, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    Mol Psychiatry 7:317-21. 2002
    ..Our results question the current reliance on plasma kinetics as the main basis for dosing regimens of antipsychotics. Studies of brain kinetics may provide a sounder basis for determining dosing schedules of psychotropic medications...
  25. ncbi request reprint Serotonin 5-HT1A receptor binding potential declines with age as measured by [11C]WAY-100635 and PET
    J Tauscher
    PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Neuropsychopharmacology 24:522-30. 2001
    ..Hence, careful age matching may be recommended for future studies using PET and [11C]WAY-100635 to examine 5-HT1A receptors...
  26. ncbi request reprint Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficient
    S Kapur
    Schizophrenia Program, University of Toronto, Toronto, Canada
    Biol Psychiatry 50:873-83. 2001
    ....
  27. ncbi request reprint Are animal studies of antipsychotics appropriately dosed? Lessons from the bedside to the bench
    S Kapur
    PET Centre, Centre for Addiction and Mental Health, Toronto, ON
    Can J Psychiatry 45:241-6. 2000
    ..We exemplify how this dosing confounder could lead to inappropriate conclusions. Data from the bedside translated to the bench--using D2 occupancy as a mediating variable--will lead to more valid animal models...
  28. ncbi request reprint Antipsychoticlike effects of amoxapine, without catalepsy, using the prepulse inhibition of the acoustic startle reflex test in rats
    M G Wadenberg
    Centre for Addiction and Mental Health, Toronto, Canada
    Biol Psychiatry 47:670-6. 2000
    ..A similar deficit can be produced by dopamine (DA) and by 5-HT(2A/C) receptor agonists in rats. Antipsychotic compounds reverse this effect...
  29. ncbi request reprint Dopamine D2 receptors internalize in their low-affinity state
    F Ko
    Department of Pharmacology, Medical Science Building, Room 4344, University of Toronto, Toronto, Ont M5S 1A8
    Neuroreport 13:1017-20. 2002
    ....
  30. ncbi request reprint Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats
    M L Wadenberg
    Section of Biopsychology, CAMH, University of Toronto, Canada
    Psychopharmacology (Berl) 150:422-9. 2000
    ..However, the quantitative relationship between striatal D2 occupancy and effects in these models is not known...
  31. ncbi request reprint Is amoxapine an atypical antipsychotic? Positron-emission tomography investigation of its dopamine2 and serotonin2 occupancy
    S Kapur
    Clarke Institute of Psychiatry, Center for Addictions and Mental Health, Toronto, Ontario, Canada
    Biol Psychiatry 45:1217-20. 1999
    ..A review of pharmacologic and behavioral data suggested that amoxapine should also conform to this profile; therefore, we undertook a positron-emission tomography (PET) study of its 5-HT2 and D2 occupancy...
  32. ncbi request reprint In vivo evidence for dopamine-mediated internalization of D2-receptors after amphetamine: differential findings with [3H]raclopride versus [3H]spiperone
    W Sun
    PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Mol Pharmacol 63:456-62. 2003
    ....
  33. ncbi request reprint Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans
    N P L G Verhoeff
    Kunin Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
    Mol Psychiatry 7:233, 322-8. 2002
    ..Thus, while DA depletion "uncovers" D(2)receptors, it does not do so for D(1) receptors. The implications of this finding for measuring endogenous DA and its effects on in vivo receptor binding in humans are discussed...
  34. ncbi request reprint 5-HT2 antagonism and EPS benefits: is there a causal connection?
    S Kapur
    PET Centre, Clark Institute of Psychiatry, Toronto, Canada
    Psychopharmacology (Berl) 124:35-9. 1996
    ..The implications of these findings for the next generation of combined 5-HT2/D2 antagonists are discussed...
  35. ncbi request reprint Pharmacotherapy of first-episode schizophrenia
    G Remington
    Department of Psychiatry, University of Toronto, Canada
    Br J Psychiatry Suppl 172:66-70. 1998
    ..A growing interest in first-episode schizophrenia reflects the belief that this line of investigation will lead to further developments regarding schizophrenia's aetiology, course and outcome...
  36. ncbi request reprint Atypical antipsychotics: are some more atypical than others?
    G Remington
    Schizophrenia Program, Centre for Addiction and Mental Health, Clarke Division, 250 College Street, Toronto, Ontario, Canada M5T 1R8
    Psychopharmacology (Berl) 148:3-15. 2000
    ..The precise pharmacologic mechanisms underlying "atypicality" remain unclear, but several conceptual frameworks are highlighted that characterize, and perhaps differentiate, these newer agents...
  37. ncbi request reprint The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study
    J H Meyer
    Clarke Division, Centre for Addictions and Mental Health, Department ofPsychiatry, University of Toronto, Ontario, Canada
    Am J Psychiatry 158:78-85. 2001
    ..The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients...
  38. ncbi request reprint The amphetamine-induced sensitized state as a model of schizophrenia
    R E Featherstone
    Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8
    Prog Neuropsychopharmacol Biol Psychiatry 31:1556-71. 2007
    ..It is concluded that amphetamine sensitization likely impacts behaviour by altering the functioning of mesolimbic dopamine systems and prefrontal cortical function and can serve as a model of certain domains of schizophrenia...
  39. ncbi request reprint Neuromodulation of frontal and temporal cortex by intravenous d-fenfluramine: an [15O]H2O PET study in humans
    J H Meyer
    Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, Ontario, Canada
    Neurosci Lett 207:25-8. 1996
    ..These results support further investigation with intravenous d-fenfluramine to study the net functional effects of serotonergic stimulation in health and illness...
  40. ncbi request reprint SB-277011 GlaxoSmithKline
    G Remington
    Center for Addiction and Mental Health, Toronto, Ontario, Canada
    Curr Opin Investig Drugs 2:946-9. 2001
    ....
  41. ncbi request reprint The effects of divided attention on encoding- and retrieval-related brain activity: A PET study of younger and older adults
    N D Anderson
    University of Toronto and Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
    J Cogn Neurosci 12:775-92. 2000
    ....
  42. ncbi request reprint Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studies
    J Tauscher
    Schizophrenia PET program, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    CNS Drugs 15:671-8. 2001
    ..This seems to be particularly important in individuals experiencing a first episode of schizophrenia, as they appear to be especially responsive to pharmacotherapy and quite sensitive to adverse effects...
  43. ncbi request reprint Dopamine D(2) receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects
    M L Wadenberg
    Schizophrenia Program, PET Center, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada
    Neuropsychopharmacology 25:633-41. 2001
    ..The implications of this finding for understanding antipsychotic action as well as the continued use of these models in drug discovery is discussed...
  44. ncbi request reprint Cerebral gray matter volume deficits in first episode psychosis
    R B Zipursky
    Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto School of Medicine, Ontario, Canada
    Arch Gen Psychiatry 55:540-6. 1998
    ..We hypothesized that deficits in gray matter volume would be present in patients presenting with a first episode of nonaffective psychosis...
  45. ncbi request reprint A positron emission tomography study of silent and oral single word reading in stuttering and nonstuttering adults
    L F De Nil
    Department of Speech Language Pathology, University of Toronto, The Toronto Western Hospital, Ontario, Canada
    J Speech Lang Hear Res 43:1038-53. 2000
    ..The results of the present study provide qualified support for the hypothesis that stuttering adults show atypical lateralization of language processes...
  46. ncbi request reprint Amoxapine shows an antipsychotic effect but worsens motor function in patients with Parkinson's disease and psychosis
    D S Sa
    Movement Disorders Unit, Division of Neurology, Toronto Western Hospital, ON, Canada
    Clin Neuropharmacol 24:242-4. 2001
    ..Therefore, although we found some support for amoxapine having antipsychotic properties, this drug seems to carry a risk of worsening motor function in patients with PD...
  47. ncbi request reprint Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response--a double-blind PET study in schizophrenia
    Ofer Agid
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1209-15. 2007
    ....
  48. ncbi request reprint Evaluation of N-desmethylclozapine as a potential antipsychotic--preclinical studies
    Sridhar Natesan
    1Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1540-9. 2007
    ....
  49. ncbi request reprint In vivo characterization of the pharmacokinetics and pharmacological properties of [11C]-(+)-PHNO in rats using an intracerebral beta-sensitive system
    Laurent Galineau
    The Vivian Rakoff Positron Emission Tomography Unit, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Synapse 60:172-83. 2006
    ..These results substantiate the use of [11C]-(+)-PHNO as an agonist radiotracer for D2-imaging. The sensitivity of its binding to competition with endogenous DA suggests an association with the subset of high affinity state D2-receptors...
  50. ncbi request reprint Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models
    Sridhar Natesan
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 31:1854-63. 2006
    ..Partial agonism of aripiprazole offers a good explanation for this dissociation and provides a framework for understanding occupancy-functional relationships of partial D2 agonist antipsychotics...
  51. ncbi request reprint Linking animal models of psychosis to computational models of dopamine function
    Andrew J Smith
    Bentley Heath, Solihull, West Midlands, UK
    Neuropsychopharmacology 32:54-66. 2007
    ..The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations...
  52. ncbi request reprint The dopamine stabilizers (S)-(-)-(3-methanesulfonyl-phenyl)-1-propyl-piperidine [(-)-OSU6162] and 4-(3-methanesulfonylphenyl)-1-propyl-piperidine (ACR16) show high in vivo D2 receptor occupancy, antipsychotic-like efficacy, and low potential for motor sid
    Sridhar Natesan
    Schizophrenia Program and PET Centre, Toronto, Ontario, Canada
    J Pharmacol Exp Ther 318:810-8. 2006
    ..The results suggest that dopamine stabilizers exhibit locomotor stabilizing as well as antipsychotic-like effects, with low motor side effect liability, in a dose range that corresponds to high D2 in vivo occupancy...
  53. ncbi request reprint Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography
    Nathalie Ginovart
    The Vivian Rakoff Positron Emission Tomography Unit, Center for Addiction and Mental Health, Toronto, Canada
    J Neurochem 97:1089-103. 2006
    ....
  54. ncbi request reprint A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone
    Gary Remington
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ont M5T 1R8, Canada
    Am J Psychiatry 163:396-401. 2006
    ..The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks...
  55. ncbi request reprint Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis
    Robert B Zipursky
    Department of Psychiatry, University of Toronto, Ontario
    Can J Psychiatry 50:462-9. 2005
    ..We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy...
  56. ncbi request reprint Increased dopamine D2(High) receptors in amphetamine-sensitized rats, measured by the agonist [(3)H](+)PHNO
    Philip Seeman
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Synapse 61:263-7. 2007
    ..2-3.5-fold increase of DA D2(High) receptors may explain why amphetamine-sensitized animals are much more sensitive to DA agonists, even though the total density of D2 receptors may apparently be unchanged or even decreased...
  57. ncbi request reprint Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia
    Hiroyuki Uchida
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    J Clin Psychiatry 69:1281-6. 2008
    ..The objective of this positron emission tomography (PET) study was to examine the striatal dopamine D(2) binding of long-acting risperidone administered intramuscularly once a month...
  58. ncbi request reprint Quetiapine extended-release versus immediate-release formulation: a positron emission tomography study
    David C Mamo
    Centre for Addiction and Mental Health, PET Centre, Toronto, Ontario, Canada
    J Clin Psychiatry 69:81-6. 2008
    ..An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D(2) receptor binding between the IR and XR formulations...
  59. doi request reprint Less is more: antipsychotic drug effects are greater with transient rather than continuous delivery
    Anne Noël Samaha
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Biol Psychiatry 64:145-52. 2008
    ..Based on prior data, we predicted that variations in the within-day kinetics of antipsychotic drug delivery would produce different outcomes, even if we held achieved dose, route, and total duration of treatment constant...
  60. ncbi request reprint 'Jumping to conclusions' and delusions in psychosis: relationship and response to treatment
    Mahesh Menon
    Schizophrenia Program and PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Canada
    Schizophr Res 98:225-31. 2008
    ..The findings suggest that JTC might moderate the effects of treatment on symptomatology, but it does not mediate the treatment induced reduction in delusional intensity...
  61. ncbi request reprint Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study
    David Mamo
    Department of Psychiatry, University of Toronto, Toronto, Canada
    Am J Psychiatry 164:1411-7. 2007
    ..The authors conducted a positron emission tomography (PET) study to characterize the simultaneous effects of aripiprazole at the D(2), 5-HT(2), and 5-HT(1A) receptors in patients with schizophrenia or schizoaffective disorder...
  62. ncbi request reprint Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans
    Ariel Graff-Guerrero
    PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Hum Brain Mapp 29:400-10. 2008
    ..This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease...
  63. ncbi request reprint D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography: an open-label study in patients with schizophrenia
    David Mamo
    Center for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 33:298-304. 2008
    ..However, supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles...
  64. ncbi request reprint Adverse subjective experience with antipsychotics and its relationship to striatal and extrastriatal D2 receptors: a PET study in schizophrenia
    Romina Mizrahi
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5S 2S1
    Am J Psychiatry 164:630-7. 2007
    ..The authors present the first double-blind controlled study to examine the relationship between striatal and extrastriatal dopamine D(2) receptor binding potential and occupancy values and adverse subjective experience...
  65. ncbi request reprint "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time
    Anne Noël Samaha
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
    J Neurosci 27:2979-86. 2007
    ..These findings provide a model and a mechanism for antipsychotic treatment failure and suggest new directions for the development of more effective antipsychotics...
  66. ncbi request reprint From dopamine to salience to psychosis--linking biology, pharmacology and phenomenology of psychosis
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada
    Schizophr Res 79:59-68. 2005
    ..The article discusses the caveats, limitations as well as the clinical implications of the salience framework...
  67. ncbi request reprint Evidence for onset of antipsychotic effects within the first 24 hours of treatment
    Shitij Kapur
    Centre for Addiction and Mental Health, 250 College St, Toronto, Ont, Canada M5R 1T8
    Am J Psychiatry 162:939-46. 2005
    ..Recent research has shown that antipsychotic action begins within the first week. The authors tested the hypothesis that psychosis improves within the first 24 hours of antipsychotic treatment...
  68. ncbi request reprint Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade
    Sitra Tauscher-Wisniewski
    Schizophrenia and Continuing Care Program, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada
    J Clin Psychiatry 63:992-7. 2002
    ..We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response...
  69. ncbi request reprint Amphetamine-sensitized animals show a sensorimotor gating and neurochemical abnormality similar to that of schizophrenia
    Catherine C Tenn
    Schizophrenia PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Schizophr Res 64:103-14. 2003
    ....
  70. ncbi request reprint The relationship between dopamine D2 receptor occupancy and the vacuous chewing movement syndrome in rats
    Peter Turrone
    Centre for Addiction and Mental Health, Schizophrenia and Continuing Care Program, 250 College Street, Room 745, Toronto, Ontario, Canada M5T 1R8
    Psychopharmacology (Berl) 165:166-71. 2003
    ..A dose-response relationship between dopamine D(2) occupancy and acute extrapyramidal symptoms (EPS) has been well established. However, the link with the induction of tardive dyskinesia (TD) is less clear...
  71. ncbi request reprint Effect of acute antipsychotic administration on dopamine synthesis in rodents and human subjects using 6-[18F]-L-m-tyrosine
    David Mamo
    Department of Psychiatry, University of Toronto, Canada
    Synapse 52:153-62. 2004
    ..Our results suggest that 6-[18F]-L-m-tyrosine PET may not be a useful tool in the study of the effect of antipsychotics on dopamine synthesis in human subjects...
  72. ncbi request reprint Amphetamine-sensitized animals show a marked increase in dopamine D2 high receptors occupied by endogenous dopamine, even in the absence of acute challenges
    Philip Seeman
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Synapse 46:235-9. 2002
    ....
  73. ncbi request reprint A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone
    David Mamo
    Department of Psychiatry, University of Toronto, Montreal, Canada
    Am J Psychiatry 161:818-25. 2004
    ..The affinity of ziprasidone for these receptors in vivo in patients was examined in a positron emission tomography (PET) study...
  74. ncbi request reprint Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics
    Johannes Tauscher
    University of Toronto Department of Psychiatry, Schizophrenia Program
    Am J Psychiatry 161:1620-5. 2004
    ....
  75. ncbi request reprint Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats
    Peter Turrone
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    Biol Psychiatry 57:406-11. 2005
    ..The objective of this study was to determine whether continuous, versus intermittent, olanzapine (OLZ) infusion differently affects the development of VCMs...
  76. ncbi request reprint Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography
    Alan A Wilson
    PET Centre, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada
    J Med Chem 48:4153-60. 2005
    ....
  77. ncbi request reprint A putative animal model of the "prodromal" state of schizophrenia
    Catherine C Tenn
    Schizophrenia PET Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto Canada
    Biol Psychiatry 57:586-93. 2005
    ..The objective of this study was to develop a putative model of the prodrome and study the effects of medications on it...
  78. ncbi request reprint Contrasting loxapine to its isomer isoloxapine--the critical role of in vivo D2 blockade in determining atypicality
    Sridhar Natesan
    Schizophrenia PET program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada, M5T 1R8
    Schizophr Res 77:189-99. 2005
    ..The purpose of this study was to systematically compare the two drugs in in vitro and in vivo animal models, and to understand mechanisms underlying their differential typical/atypical profiles...
  79. ncbi request reprint Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action
    Shitij Kapur
    Department of Psychiatry, University of Toronto, Toronto M5S 3H6, Canada
    Neuroreport 13:831-5. 2002
    ..The implications for the design of future antipsychotics is discussed...
  80. ncbi request reprint Elevation of prolactin levels by atypical antipsychotics
    Peter Turrone
    Department of Psychiatry, University of Toronto, Ont, Canada
    Am J Psychiatry 159:133-5. 2002
    ..Atypical antipsychotics are thought not to elevate prolactin levels. The authors examined data suggesting that atypical antipsychotics do elevate prolactin levels but more transiently than typical antipsychotics...
  81. ncbi request reprint Clozapine can induce high dopamine D(2) receptor occupancy in vivo
    Tetsuya Suhara
    Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan
    Psychopharmacology (Berl) 160:107-12. 2002
    ..Furthermore, even at maximum occupancy, 70% is not exceeded. Several mechanisms have been proposed as explanations for this low D(2) receptor occupancy, but clear evidence is limited...
  82. ncbi request reprint Dopamine D2 receptor radiotracers [(11)C](+)-PHNO and [(3)H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo
    Patrick N McCormick
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Nucl Med Biol 35:11-7. 2008
    ....
  83. ncbi request reprint The formation of abnormal associations in schizophrenia: neural and behavioral evidence
    Jimmy Jensen
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 33:473-9. 2008
    ..The aberrant activations and response are consistent with the idea that patients aberrantly assign motivational salience to neutral stimuli, and this process may be one of the aberrations that predisposes them to psychosis...
  84. ncbi request reprint Early use of clozapine for poorly responding first-episode psychosis
    Ofer Agid
    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    J Clin Psychopharmacol 27:369-73. 2007
    ....
  85. ncbi request reprint Amoxapine shows atypical antipsychotic effects in patients with schizophrenia: results from a prospective open-label study
    Rogelio Apiquian
    Carracci Medical Group, Mexico City, Mexico
    Schizophr Res 59:35-9. 2003
    ..To examine if this leads to an atypical antipsychotic effect in the clinical context, the authors examined the antipsychotic and side-effect profile of amoxapine in acutely psychotic patients with schizophrenia...
  86. ncbi request reprint Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635
    Johannes Tauscher
    PET Centre, Toronto, Ontario
    Arch Gen Psychiatry 59:514-20. 2002
    ....
  87. ncbi request reprint Amoxapine as an antipsychotic: comparative study versus haloperidol
    Imran B Chaudhry
    University of Manchester, Manchester, UK
    J Clin Psychopharmacol 27:575-81. 2007
    ..However, it did not prove to have fewer extrapyramidal side effects than haloperidol, possibly because the baseline scores were very low...
  88. ncbi request reprint Amoxapine as an atypical antipsychotic: a comparative study vs risperidone
    Rogelio Apiquian
    Department of Psychiatry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Av Insurgentes Sur 3877, Mexico City, 14296 Mexico
    Neuropsychopharmacology 30:2236-44. 2005
    ..Since amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotics, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics...
  89. ncbi request reprint First human evidence of d-amphetamine induced displacement of a D2/3 agonist radioligand: A [11C]-(+)-PHNO positron emission tomography study
    Matthaus Willeit
    Positron Emission Tomography Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
    Neuropsychopharmacology 33:279-89. 2008
    ..11)C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D(2/3) antagonist radioligands...
  90. ncbi request reprint Anesthetics inhibit high-affinity states of dopamine D2 and other G-linked receptors
    Philip Seeman
    Department of Pharmacology, University of Toronto, Toronto, Ontario M5S JA8, Canada
    Synapse 50:35-40. 2003
    ....
  91. ncbi request reprint Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D1 receptor agonist injected into the medial prefrontal cortex
    Paul J Fletcher
    Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
    Psychopharmacology (Berl) 183:190-200. 2005
    ..These disorders are characterized by cognitive deficits, particularly in prefrontally mediated executive function...
  92. ncbi request reprint Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation
    Zafiris J Daskalakis
    Schizophrenia and Continuing Care Program, Centre for Addiction and Mental Health, Department of Psychiatry, Toronto Western General Hospital, University of Toronto, Ontario, Canada
    Arch Gen Psychiatry 59:347-54. 2002
    ....
  93. ncbi request reprint Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition
    Catherine C Tenn
    Schizophrenia PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Psychopharmacology (Berl) 180:366-76. 2005
    ..amphetamine, Amp) and glutamatergic (e.g., phencyclidine, PCP) function. In addition to exerting short-term acute effects, these agents also induce long-term effects, as seen, for example, in neurochemical and behavioural sensitization...
  94. ncbi request reprint Dopamine, prediction error and associative learning: a model-based account
    Andrew Smith
    Department of Psychology, Neuroscience and Behaviour, McMaster University, Hamilton, Ontario, Canada
    Network 17:61-84. 2006
    ..The model distinguishes itself from existing accounts by offering novel predictions pertaining to the firing of dopamine neurons in various untested behavioral scenarios...
  95. ncbi request reprint How antipsychotics become anti-"psychotic"--from dopamine to salience to psychosis
    Shitij Kapur
    Centre for Addiction and Mental Health, and the University of Toronto, 33 Russell Street Toronto, Ontario M5S 2S1, Canada
    Trends Pharmacol Sci 25:402-6. 2004
    ..The implications of this framework for relapse and other clinical phenomena, animal models and future studies are discussed...
  96. ncbi request reprint A model of anticholinergic activity of atypical antipsychotic medications
    Marci L Chew
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Schizophr Res 88:63-72. 2006
    ..However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic...
  97. ncbi request reprint The selective effect of antipsychotics on the different dimensions of the experience of psychosis in schizophrenia spectrum disorders
    Romina Mizrahi
    CAMH, and Department of Psychiatry, Faculty of Medicine, University of Toronto, Ontario, Canada
    Schizophr Res 88:111-8. 2006
    ....
  98. ncbi request reprint Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: parallels to schizophrenia
    Robert E Featherstone
    Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:483-92. 2007
    ..These results support the notion that MAM treatment may simulate some aspects of schizophrenic cognition...
  99. ncbi request reprint A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex
    Paul J Fletcher
    Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1122-32. 2007
    ..The reversal of these deficits by a D1 receptor agonist provides further evidence that prefrontal D1 dopamine receptors are involved in cognition, and may be a potential target for treatment of impaired cognition in schizophrenia...
  100. ncbi request reprint The effect of antipsychotic treatment on Theory of Mind
    Romina Mizrahi
    Centre for Addiction and Mental Health, and Department of Psychiatry, Faculty of Medicine, University of Toronto, Ontario, Canada
    Psychol Med 37:595-601. 2007
    ..However, it remains unclear whether TOM deficits constitute a trait- or a state-related deficit and whether they respond to antipsychotic treatment, and also whether the change in TOM and change in psychosis are associated...
  101. ncbi request reprint A model of antipsychotic action in conditioned avoidance: a computational approach
    Andrew Smith
    Psychology Department, McMaster University, Hamilton, Ontario, Canada
    Neuropsychopharmacology 29:1040-9. 2004
    ..The APD action in this model is most consistent with an effect on 'expected future reward'--an idea closely linked to motivational drives and consistent with several leading theories of dopamine action...