The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Christer Halldin - One of the best experts on this subject based on the ideXlab platform.
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PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain.
The international journal of neuropsychopharmacology, 2007Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Mattias Månsson, Hristina Jovanovic, Per Karlsson, Kimberly E. Vanover, Uli Hacksell, Mark R. Brann, Robert E. DavisAbstract:The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated, in part, by interactions with the 5-HT2A receptor. Recently, it has been recognized that clinically effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists. In the present study, which is part of the clinical development of the novel, selective 5-HT2A receptor inverse agonist ACP-103, we applied positron emission tomography (PET) with the radioligand [11C]N-Methylspiperone ([11C]NMSP) to study the relationship between oral dose, plasma level, and uptake of ACP-103 in living human brain. The safety of drug administration was also assessed. Four healthy volunteers were examined by PET at baseline, and after the oral administration of various single doses of ACP-103. Two subjects each received 1, 5, and 20 mg doses, and two subjects each received 2, 10, and 100 mg doses, respectively. ACP-103 was well tolerated. Detectable receptor binding was observed at very low ACP-103 serum levels. Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action. A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg, and reached near maximal displacement following the 10-20 mg dose. In conclusion, administration of ACP-103 to healthy volunteers was found to be safe and well tolerated, and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET.
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suggested minimal effective dose of risperidone based on pet measured d2 and 5 ht2a receptor occupancy in schizophrenic patients
American Journal of Psychiatry, 1999Co-Authors: Svante Nyberg, Christer Halldin, Bo Eriksson, Gabriella Oxenstierna, Lars FardeAbstract:OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range=79%–85%), 5-HT2A receptor occupanc...
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Central 5-HT2A and D2 dopamine receptor occupancy after sublingual administration of ORG 5222 in healthy men
Psychopharmacology, 1997Co-Authors: Bengt Andrée, Christer Halldin, Maria Vrijmoed-de Vries, Lars FardeAbstract:It has been suggested that a combined blockade of 5-HT2A and D2-dopamine receptors improves efficacy and reduces the risk for extrapyramidal symptoms when treating schizophrenic patients with antipsychotic drugs. ORG 5222 is a new potential anti-psychotic drug which has high affinity for 5-HT2A, D2-dopamine and α1 adrenergic receptors in vitro. The objective of this study was to examine if ORG 5222 occupies 5-HT2A and D2-dopamine receptors in human subjects in vivo. Central receptor occupancy was measured by positron emission tomography (PET) in three healthy subjects after sublingual administration of 100 μg ORG 5222. [11C]N-Methylspiperone ([11C] NMSP) was the radioligand used to measure 5-HT2A receptor binding in the neocortex and [11C]raclopride to measure D2-dopamine receptor binding in the striatum. The 5-HT2A occupancy was 15–30% and the D2-dopamine receptor occupancy was 12–23%. The study confirms that ORG 5222 binds to 5-HT2A and D2-dopamine receptors in human brain. Since receptor occupancy of ORG 5222 is rather low, doses higher than 100 μg are suggested in future clinical trials to evaluate the antipsychotic drug effect of ORG 5222.
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No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]N-Methylspiperone.
Psychiatry research, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Lars Eriksson, Christer HalldinAbstract:The dopamine hypothesis of schizophrenia received strong support when a two- to three-fold elevation of D2 receptor densities was demonstrated by positron emission tomography (PET) and [11C]N-Methylspiperone ([11C]NMSP). In the present study, the reproducibility of this finding was examined by application of a similar method in seven normal comparison subjects and seven neuroleptic-naive schizophrenic patients examined by PET before and after administration of haloperidol, 7.5 mg. After haloperidol, the specific binding of [11C]NMSP was reduced by 80-90%, resulting in a signal-to-noise ratio that was unfavorably low for reliable quantification. No significant difference was found between normal subjects and patients in a descriptive analysis of the time-activity curves or in a nonequilibrium graphical determination of D2 receptor densities in the basal ganglia. The results are consistent with those of a previous quantitative PET study of [11C]raclopride binding, which showed normal densities of D2 receptors in the striatum of neuroleptic-naive schizophrenic patients.
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D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients.
The American journal of psychiatry, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Svante Nyberg, Per Karlsson, Göran SedvallAbstract:Objective: Central D,, D2, and 5-HT2 receptor occupancy in schizophrenic patients treated with clozapine was determined and related to clozapine serum concentrations. Method: Sev- enteen patients treated with clozapine (125-600 mg/day) were examined with positron emission tomography (PET) and one to three of the following selective radioligands: ("CjSCH23390 (N=1 1), ("CJraclopride (N=16), and ("C)N-Methylspiperone (N=5). Cloza- pine concentration in serum was determined by gas chromatography/mass spectrometry. � �.LL1tD2 receptor occupancy (20%-67%) was lower than that previously determined in pa- tients treated with classicalneuroleptics (70%-90%). D, receptor occupancy (36%-59%) was higher than that induced by classical neuroleptics (0%-44%). 5-HT2 receptor occupancy was very high (84%-94%), even at low clozapine doses. Despite a 20-fold range in clozapine serum concentration (1 05-2 12 1 ng/ml) at the time of PET examination, D2 receptor occupancy was low in all patients and was not described by the curvilinear relationship between serum drug concentration and receptor occupancy that has been demonstrated for classical antipsychotics. Conclusions: The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extra- pyramidal side effects. The combination of relatively high D1, low D2, and very high 5-HT2 receptor occupancy values is unique to clozapine. Clozapine serum concentrations have not been unequivocally shown to predict clinicaleffects. In this study, concentration did not predict degree ofoccupancy in brain. Thus, careful clinical titration cannot be replaced by monitoring of drug concentrations for optimization of clozapine treatment in individual patients. (AmJ Psychiatry 1995; 152:1444-1449)
Lars Farde - One of the best experts on this subject based on the ideXlab platform.
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PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain.
The international journal of neuropsychopharmacology, 2007Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Mattias Månsson, Hristina Jovanovic, Per Karlsson, Kimberly E. Vanover, Uli Hacksell, Mark R. Brann, Robert E. DavisAbstract:The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated, in part, by interactions with the 5-HT2A receptor. Recently, it has been recognized that clinically effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists. In the present study, which is part of the clinical development of the novel, selective 5-HT2A receptor inverse agonist ACP-103, we applied positron emission tomography (PET) with the radioligand [11C]N-Methylspiperone ([11C]NMSP) to study the relationship between oral dose, plasma level, and uptake of ACP-103 in living human brain. The safety of drug administration was also assessed. Four healthy volunteers were examined by PET at baseline, and after the oral administration of various single doses of ACP-103. Two subjects each received 1, 5, and 20 mg doses, and two subjects each received 2, 10, and 100 mg doses, respectively. ACP-103 was well tolerated. Detectable receptor binding was observed at very low ACP-103 serum levels. Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action. A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg, and reached near maximal displacement following the 10-20 mg dose. In conclusion, administration of ACP-103 to healthy volunteers was found to be safe and well tolerated, and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET.
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suggested minimal effective dose of risperidone based on pet measured d2 and 5 ht2a receptor occupancy in schizophrenic patients
American Journal of Psychiatry, 1999Co-Authors: Svante Nyberg, Christer Halldin, Bo Eriksson, Gabriella Oxenstierna, Lars FardeAbstract:OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range=79%–85%), 5-HT2A receptor occupanc...
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Central 5-HT2A and D2 dopamine receptor occupancy after sublingual administration of ORG 5222 in healthy men
Psychopharmacology, 1997Co-Authors: Bengt Andrée, Christer Halldin, Maria Vrijmoed-de Vries, Lars FardeAbstract:It has been suggested that a combined blockade of 5-HT2A and D2-dopamine receptors improves efficacy and reduces the risk for extrapyramidal symptoms when treating schizophrenic patients with antipsychotic drugs. ORG 5222 is a new potential anti-psychotic drug which has high affinity for 5-HT2A, D2-dopamine and α1 adrenergic receptors in vitro. The objective of this study was to examine if ORG 5222 occupies 5-HT2A and D2-dopamine receptors in human subjects in vivo. Central receptor occupancy was measured by positron emission tomography (PET) in three healthy subjects after sublingual administration of 100 μg ORG 5222. [11C]N-Methylspiperone ([11C] NMSP) was the radioligand used to measure 5-HT2A receptor binding in the neocortex and [11C]raclopride to measure D2-dopamine receptor binding in the striatum. The 5-HT2A occupancy was 15–30% and the D2-dopamine receptor occupancy was 12–23%. The study confirms that ORG 5222 binds to 5-HT2A and D2-dopamine receptors in human brain. Since receptor occupancy of ORG 5222 is rather low, doses higher than 100 μg are suggested in future clinical trials to evaluate the antipsychotic drug effect of ORG 5222.
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No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]N-Methylspiperone.
Psychiatry research, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Lars Eriksson, Christer HalldinAbstract:The dopamine hypothesis of schizophrenia received strong support when a two- to three-fold elevation of D2 receptor densities was demonstrated by positron emission tomography (PET) and [11C]N-Methylspiperone ([11C]NMSP). In the present study, the reproducibility of this finding was examined by application of a similar method in seven normal comparison subjects and seven neuroleptic-naive schizophrenic patients examined by PET before and after administration of haloperidol, 7.5 mg. After haloperidol, the specific binding of [11C]NMSP was reduced by 80-90%, resulting in a signal-to-noise ratio that was unfavorably low for reliable quantification. No significant difference was found between normal subjects and patients in a descriptive analysis of the time-activity curves or in a nonequilibrium graphical determination of D2 receptor densities in the basal ganglia. The results are consistent with those of a previous quantitative PET study of [11C]raclopride binding, which showed normal densities of D2 receptors in the striatum of neuroleptic-naive schizophrenic patients.
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D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients.
The American journal of psychiatry, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Svante Nyberg, Per Karlsson, Göran SedvallAbstract:Objective: Central D,, D2, and 5-HT2 receptor occupancy in schizophrenic patients treated with clozapine was determined and related to clozapine serum concentrations. Method: Sev- enteen patients treated with clozapine (125-600 mg/day) were examined with positron emission tomography (PET) and one to three of the following selective radioligands: ("CjSCH23390 (N=1 1), ("CJraclopride (N=16), and ("C)N-Methylspiperone (N=5). Cloza- pine concentration in serum was determined by gas chromatography/mass spectrometry. � �.LL1tD2 receptor occupancy (20%-67%) was lower than that previously determined in pa- tients treated with classicalneuroleptics (70%-90%). D, receptor occupancy (36%-59%) was higher than that induced by classical neuroleptics (0%-44%). 5-HT2 receptor occupancy was very high (84%-94%), even at low clozapine doses. Despite a 20-fold range in clozapine serum concentration (1 05-2 12 1 ng/ml) at the time of PET examination, D2 receptor occupancy was low in all patients and was not described by the curvilinear relationship between serum drug concentration and receptor occupancy that has been demonstrated for classical antipsychotics. Conclusions: The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extra- pyramidal side effects. The combination of relatively high D1, low D2, and very high 5-HT2 receptor occupancy values is unique to clozapine. Clozapine serum concentrations have not been unequivocally shown to predict clinicaleffects. In this study, concentration did not predict degree ofoccupancy in brain. Thus, careful clinical titration cannot be replaced by monitoring of drug concentrations for optimization of clozapine treatment in individual patients. (AmJ Psychiatry 1995; 152:1444-1449)
Anna-lena Nordström - One of the best experts on this subject based on the ideXlab platform.
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PET analysis of the 5-HT2A receptor inverse agonist ACP-103 in human brain.
The international journal of neuropsychopharmacology, 2007Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Mattias Månsson, Hristina Jovanovic, Per Karlsson, Kimberly E. Vanover, Uli Hacksell, Mark R. Brann, Robert E. DavisAbstract:The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated, in part, by interactions with the 5-HT2A receptor. Recently, it has been recognized that clinically effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists. In the present study, which is part of the clinical development of the novel, selective 5-HT2A receptor inverse agonist ACP-103, we applied positron emission tomography (PET) with the radioligand [11C]N-Methylspiperone ([11C]NMSP) to study the relationship between oral dose, plasma level, and uptake of ACP-103 in living human brain. The safety of drug administration was also assessed. Four healthy volunteers were examined by PET at baseline, and after the oral administration of various single doses of ACP-103. Two subjects each received 1, 5, and 20 mg doses, and two subjects each received 2, 10, and 100 mg doses, respectively. ACP-103 was well tolerated. Detectable receptor binding was observed at very low ACP-103 serum levels. Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action. A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg, and reached near maximal displacement following the 10-20 mg dose. In conclusion, administration of ACP-103 to healthy volunteers was found to be safe and well tolerated, and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET.
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No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]N-Methylspiperone.
Psychiatry research, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Lars Eriksson, Christer HalldinAbstract:The dopamine hypothesis of schizophrenia received strong support when a two- to three-fold elevation of D2 receptor densities was demonstrated by positron emission tomography (PET) and [11C]N-Methylspiperone ([11C]NMSP). In the present study, the reproducibility of this finding was examined by application of a similar method in seven normal comparison subjects and seven neuroleptic-naive schizophrenic patients examined by PET before and after administration of haloperidol, 7.5 mg. After haloperidol, the specific binding of [11C]NMSP was reduced by 80-90%, resulting in a signal-to-noise ratio that was unfavorably low for reliable quantification. No significant difference was found between normal subjects and patients in a descriptive analysis of the time-activity curves or in a nonequilibrium graphical determination of D2 receptor densities in the basal ganglia. The results are consistent with those of a previous quantitative PET study of [11C]raclopride binding, which showed normal densities of D2 receptors in the striatum of neuroleptic-naive schizophrenic patients.
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D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients.
The American journal of psychiatry, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Svante Nyberg, Per Karlsson, Göran SedvallAbstract:Objective: Central D,, D2, and 5-HT2 receptor occupancy in schizophrenic patients treated with clozapine was determined and related to clozapine serum concentrations. Method: Sev- enteen patients treated with clozapine (125-600 mg/day) were examined with positron emission tomography (PET) and one to three of the following selective radioligands: ("CjSCH23390 (N=1 1), ("CJraclopride (N=16), and ("C)N-Methylspiperone (N=5). Cloza- pine concentration in serum was determined by gas chromatography/mass spectrometry. � �.LL1tD2 receptor occupancy (20%-67%) was lower than that previously determined in pa- tients treated with classicalneuroleptics (70%-90%). D, receptor occupancy (36%-59%) was higher than that induced by classical neuroleptics (0%-44%). 5-HT2 receptor occupancy was very high (84%-94%), even at low clozapine doses. Despite a 20-fold range in clozapine serum concentration (1 05-2 12 1 ng/ml) at the time of PET examination, D2 receptor occupancy was low in all patients and was not described by the curvilinear relationship between serum drug concentration and receptor occupancy that has been demonstrated for classical antipsychotics. Conclusions: The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extra- pyramidal side effects. The combination of relatively high D1, low D2, and very high 5-HT2 receptor occupancy values is unique to clozapine. Clozapine serum concentrations have not been unequivocally shown to predict clinicaleffects. In this study, concentration did not predict degree ofoccupancy in brain. Thus, careful clinical titration cannot be replaced by monitoring of drug concentrations for optimization of clozapine treatment in individual patients. (AmJ Psychiatry 1995; 152:1444-1449)
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High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET
Psychopharmacology, 1993Co-Authors: Anna-lena Nordström, Lars Farde, Christer HalldinAbstract:The clinical benefit of the atypical antipsychotic drug clozapine may be related to a combined effect on D2 and 5-HT2 receptors. To examine the basis for this hypothesis, positron emission tomography (PET) and the radioligand [11C]N-Methylspiperone were used to determine cortical 5-HT2 receptor occupancy in three psychotic patients treated with 125 mg, 175 mg and 200 mg clozapine daily. The uptake of [11C]N-Methylspiperone in the frontal cortex was very low compared to that in neuroleptic naive schizophrenic patients. 5-HT2 receptor occupancy calculated in the clozapine treated patients was 84%, 87% and 90%. The results show that clinical treatment with clozapine induces a high 5-HT2 receptor occupancy in psychotic patients at a low dose level.
Svante Nyberg - One of the best experts on this subject based on the ideXlab platform.
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suggested minimal effective dose of risperidone based on pet measured d2 and 5 ht2a receptor occupancy in schizophrenic patients
American Journal of Psychiatry, 1999Co-Authors: Svante Nyberg, Christer Halldin, Bo Eriksson, Gabriella Oxenstierna, Lars FardeAbstract:OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range=79%–85%), 5-HT2A receptor occupanc...
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D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients.
The American journal of psychiatry, 1995Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Svante Nyberg, Per Karlsson, Göran SedvallAbstract:Objective: Central D,, D2, and 5-HT2 receptor occupancy in schizophrenic patients treated with clozapine was determined and related to clozapine serum concentrations. Method: Sev- enteen patients treated with clozapine (125-600 mg/day) were examined with positron emission tomography (PET) and one to three of the following selective radioligands: ("CjSCH23390 (N=1 1), ("CJraclopride (N=16), and ("C)N-Methylspiperone (N=5). Cloza- pine concentration in serum was determined by gas chromatography/mass spectrometry. � �.LL1tD2 receptor occupancy (20%-67%) was lower than that previously determined in pa- tients treated with classicalneuroleptics (70%-90%). D, receptor occupancy (36%-59%) was higher than that induced by classical neuroleptics (0%-44%). 5-HT2 receptor occupancy was very high (84%-94%), even at low clozapine doses. Despite a 20-fold range in clozapine serum concentration (1 05-2 12 1 ng/ml) at the time of PET examination, D2 receptor occupancy was low in all patients and was not described by the curvilinear relationship between serum drug concentration and receptor occupancy that has been demonstrated for classical antipsychotics. Conclusions: The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extra- pyramidal side effects. The combination of relatively high D1, low D2, and very high 5-HT2 receptor occupancy values is unique to clozapine. Clozapine serum concentrations have not been unequivocally shown to predict clinicaleffects. In this study, concentration did not predict degree ofoccupancy in brain. Thus, careful clinical titration cannot be replaced by monitoring of drug concentrations for optimization of clozapine treatment in individual patients. (AmJ Psychiatry 1995; 152:1444-1449)
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5-HT_2 and D_2 dopamine receptor occupancy in the living human brain
Psychopharmacology, 1993Co-Authors: Svante Nyberg, Lars Farde, Christer Halldin, Lars Eriksson, Bo ErikssonAbstract:It has been suggested that a combined blockade of 5-HT_2 and D_2 dopamine receptors may be superior to D_2 dopamine antagonists alone in the treatment of schizophrenia. Risperidone, which has a high affinity for 5-HT_2 and D_2 dopamine receptors in vitro, is a new antipsychotic drug that has been developed according to this hypothesis. The aim of this study was to examine if risperidone indeed induces 5-HT_2 and D_2 dopamine receptor occupancy in vivo in humans. Central receptor occupancy was examined by positron emission tomography (PET) in three healthy men after oral administration of 1 mg risperidone. [^11C]N-Methylspiperone ([^11C]NMSP) was used as a radioligand for determination of 5-HT_2 receptor occupancy in the neocortex. Both an equilibrium ratio analysis and a kinetic three-compartmental analysis indicated a 5-HT_2 receptor occupancy about 60%. [^11C]raclopride was used as a radioligand for determination of D_2 dopamine receptor occupancy in the striatum and the calculated occupancy was about 50%. This is the first quantitative determination of 5-HT_2 receptor occupancy induced by an antipsychotic drug in the living human brain. The results indicate that 5-HT_2 receptor occupancy should be very high at the dose level of 4–10 mg risperidone daily, as suggested for clinical use. Risperidone is thus an appropriate compound for clinical evaluation of the benefit of combined 5-HT_2 and D_2 dopamine receptor blockade in the treatment of schizophrenia.
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5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone.
Psychopharmacology, 1993Co-Authors: Svante Nyberg, Lars Farde, Christer Halldin, Lars Eriksson, Bo ErikssonAbstract:It has been suggested that a combined blockade of 5-HT2 and D2 dopamine receptors may be superior to D2 dopamine antagonists alone in the treatment of schizophrenia. Risperidone, which has a high affinity for 5-HT2 and D2 dopamine receptors in vitro, is a new antipsychotic drug that has been developed according to this hypothesis. The aim of this study was to examine if risperidone indeed induces 5-HT2 and D2 dopamine receptor occupancy in vivo in humans. Central receptor occupancy was examined by positron emission tomography (PET) in three healthy men after oral administration of 1 mg risperidone. [11C]N-Methylspiperone ([11C]NMSP) was used as a radioligand for determination of 5-HT2 receptor occupancy in the neocortex. Both an equilibrium ratio analysis and a kinetic three-compartmental analysis indicated a 5-HT2 receptor occupancy about 60%. [11C]raclopride was used as a radioligand for determination of D2 dopamine receptor occupancy in the striatum and the calculated occupancy was about 50%. This is the first quantitative determination of 5-HT2 receptor occupancy induced by an antipsychotic drug in the living human brain. The results indicate that 5-HT2 receptor occupancy should be very high at the dose level of 4–10 mg risperidone daily, as suggested for clinical use. Risperidone is thus an appropriate compound for clinical evaluation of the benefit of combined 5-HT2 and D2 dopamine receptor blockade in the treatment of schizophrenia.
Bo Eriksson - One of the best experts on this subject based on the ideXlab platform.
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suggested minimal effective dose of risperidone based on pet measured d2 and 5 ht2a receptor occupancy in schizophrenic patients
American Journal of Psychiatry, 1999Co-Authors: Svante Nyberg, Christer Halldin, Bo Eriksson, Gabriella Oxenstierna, Lars FardeAbstract:OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range=79%–85%), 5-HT2A receptor occupanc...
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5-HT_2 and D_2 dopamine receptor occupancy in the living human brain
Psychopharmacology, 1993Co-Authors: Svante Nyberg, Lars Farde, Christer Halldin, Lars Eriksson, Bo ErikssonAbstract:It has been suggested that a combined blockade of 5-HT_2 and D_2 dopamine receptors may be superior to D_2 dopamine antagonists alone in the treatment of schizophrenia. Risperidone, which has a high affinity for 5-HT_2 and D_2 dopamine receptors in vitro, is a new antipsychotic drug that has been developed according to this hypothesis. The aim of this study was to examine if risperidone indeed induces 5-HT_2 and D_2 dopamine receptor occupancy in vivo in humans. Central receptor occupancy was examined by positron emission tomography (PET) in three healthy men after oral administration of 1 mg risperidone. [^11C]N-Methylspiperone ([^11C]NMSP) was used as a radioligand for determination of 5-HT_2 receptor occupancy in the neocortex. Both an equilibrium ratio analysis and a kinetic three-compartmental analysis indicated a 5-HT_2 receptor occupancy about 60%. [^11C]raclopride was used as a radioligand for determination of D_2 dopamine receptor occupancy in the striatum and the calculated occupancy was about 50%. This is the first quantitative determination of 5-HT_2 receptor occupancy induced by an antipsychotic drug in the living human brain. The results indicate that 5-HT_2 receptor occupancy should be very high at the dose level of 4–10 mg risperidone daily, as suggested for clinical use. Risperidone is thus an appropriate compound for clinical evaluation of the benefit of combined 5-HT_2 and D_2 dopamine receptor blockade in the treatment of schizophrenia.
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5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone.
Psychopharmacology, 1993Co-Authors: Svante Nyberg, Lars Farde, Christer Halldin, Lars Eriksson, Bo ErikssonAbstract:It has been suggested that a combined blockade of 5-HT2 and D2 dopamine receptors may be superior to D2 dopamine antagonists alone in the treatment of schizophrenia. Risperidone, which has a high affinity for 5-HT2 and D2 dopamine receptors in vitro, is a new antipsychotic drug that has been developed according to this hypothesis. The aim of this study was to examine if risperidone indeed induces 5-HT2 and D2 dopamine receptor occupancy in vivo in humans. Central receptor occupancy was examined by positron emission tomography (PET) in three healthy men after oral administration of 1 mg risperidone. [11C]N-Methylspiperone ([11C]NMSP) was used as a radioligand for determination of 5-HT2 receptor occupancy in the neocortex. Both an equilibrium ratio analysis and a kinetic three-compartmental analysis indicated a 5-HT2 receptor occupancy about 60%. [11C]raclopride was used as a radioligand for determination of D2 dopamine receptor occupancy in the striatum and the calculated occupancy was about 50%. This is the first quantitative determination of 5-HT2 receptor occupancy induced by an antipsychotic drug in the living human brain. The results indicate that 5-HT2 receptor occupancy should be very high at the dose level of 4–10 mg risperidone daily, as suggested for clinical use. Risperidone is thus an appropriate compound for clinical evaluation of the benefit of combined 5-HT2 and D2 dopamine receptor blockade in the treatment of schizophrenia.
