Research Topics
Species | S KapurSummaryCountry: Canada Publications
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Publications
High levels of dopamine D2 receptor occupancy with low-dose haloperidol treatment: a PET studyS 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...
A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancyS 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...
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...
Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophreniaS 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...
PET evidence that loxapine is an equipotent blocker of 5-HT2 and D2 receptors: implications for the therapeutics of schizophreniaS 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...
A new framework for investigating antipsychotic action in humans: lessons from PET imagingS 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...
5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigationS 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...
A voxel-by-voxel analysis of [18F]setoperone PET data shows no substantial serotonin 5-HT(2A) receptor changes in schizophreniaN 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...
The D2 receptor occupancy profile of loxapine determined using PETS 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...
Atypical antipsychotics: new directions and new challenges in the treatment of schizophreniaS 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...
D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PETG 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...
A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjectsN 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....
Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging studyJ 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...
Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapineS Kapur
PET Centre, Clarke Division, CAMH, Toronto, ONT Canada
Am J Psychiatry 158:311-4. 2001....
Serotonin 5-HT1A receptor binding potential declines with age as measured by [11C]WAY-100635 and PETJ 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...
Significant dissociation of brain and plasma kinetics with antipsychoticsJohannes 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...
Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesisS 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...
Dopamine D(2) receptors and their role in atypical antipsychotic action: still necessary and may even be sufficientS Kapur
Schizophrenia Program, University of Toronto, Toronto, Canada
Biol Psychiatry 50:873-83. 2001....
Are animal studies of antipsychotics appropriately dosed? Lessons from the bedside to the benchS 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...
Antipsychoticlike effects of amoxapine, without catalepsy, using the prepulse inhibition of the acoustic startle reflex test in ratsM 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...
The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging studyJ 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...
Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humansN 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...
Is amoxapine an atypical antipsychotic? Positron-emission tomography investigation of its dopamine2 and serotonin2 occupancyS 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...
Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in ratsM 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...
In vivo evidence for dopamine-mediated internalization of D2-receptors after amphetamine: differential findings with [3H]raclopride versus [3H]spiperoneW Sun
PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
Mol Pharmacol 63:456-62. 2003....
Dopamine D(2) receptor blockade by haloperidol. (3)H-raclopride reveals much higher occupancy than EEDQS Kapur
Schizophrenia Program, CAMH, Ontario, Toronto, Canada
Neuropsychopharmacology 23:595-8. 2000....
Dopamine D2 receptors internalize in their low-affinity stateF Ko
Department of Pharmacology, Medical Science Building, Room 4344, University of Toronto, Toronto, Ont. M5S 1A8
Neuroreport 13:1017-20. 2002....
Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic actionS 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...
Pharmacotherapy of first-episode schizophreniaG 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...
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...
Drug-induced receptor occupancy: substantial differences in measurements made in vivo vs ex vivoS 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...
Neuromodulation of frontal and temporal cortex by intravenous d-fenfluramine: an [15O]H2O PET study in humansJ 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...
NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophreniaS 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...
The amphetamine-induced sensitized state as a model of schizophreniaR 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...
SB-277011 GlaxoSmithKlineG Remington
Center for Addiction and Mental Health, Toronto, Ontario, Canada
Curr Opin Investig Drugs 2:946-9. 2001....
Choosing the right dose of antipsychotics in schizophrenia: lessons from neuroimaging studiesJ 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...
The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in ratsS 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...
The effects of divided attention on encoding- and retrieval-related brain activity: A PET study of younger and older adultsN D Anderson
University of Toronto and Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
J Cogn Neurosci 12:775-92. 2000....
Dopamine D(2) receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effectsM 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...
Cerebral gray matter volume deficits in first episode psychosisR 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...
A positron emission tomography study of silent and oral single word reading in stuttering and nonstuttering adultsL 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...
Amoxapine shows an antipsychotic effect but worsens motor function in patients with Parkinson's disease and psychosisD 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...
