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Philip H. Elsinga - One of the best experts on this subject based on the ideXlab platform.
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despite irreversible binding pet tracer 11c sa5845 is suitable for imaging of Drug Competition at sigma receptors the cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, Aren Van Waarde, Klaus L. Leenders, Paul R Maguire, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors—The cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors-the cases of ketamine and haloperidol.
Neurochemistry international, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [11C]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with +/- -ketamine. The tracer had a plasma half-life of 77+/-1.7min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, Ki, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands - -ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors.
Rudie Kortekaas - One of the best experts on this subject based on the ideXlab platform.
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despite irreversible binding pet tracer 11c sa5845 is suitable for imaging of Drug Competition at sigma receptors the cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, Aren Van Waarde, Klaus L. Leenders, Paul R Maguire, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors—The cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors-the cases of ketamine and haloperidol.
Neurochemistry international, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [11C]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with +/- -ketamine. The tracer had a plasma half-life of 77+/-1.7min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, Ki, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands - -ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors.
Aren Van Waarde - One of the best experts on this subject based on the ideXlab platform.
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despite irreversible binding pet tracer 11c sa5845 is suitable for imaging of Drug Competition at sigma receptors the cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, Aren Van Waarde, Klaus L. Leenders, Paul R Maguire, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors—The cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors-the cases of ketamine and haloperidol.
Neurochemistry international, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [11C]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with +/- -ketamine. The tracer had a plasma half-life of 77+/-1.7min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, Ki, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands - -ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors.
Klaus L. Leenders - One of the best experts on this subject based on the ideXlab platform.
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despite irreversible binding pet tracer 11c sa5845 is suitable for imaging of Drug Competition at sigma receptors the cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, Aren Van Waarde, Klaus L. Leenders, Paul R Maguire, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors—The cases of ketamine and haloperidol
Neurochemistry International, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [C-11]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with ()ketamine. The tracer had a plasma half-life of 77 +/- 1.7 min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, K-i, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands (-)-ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors. (c) 2008 Elsevier Ltd. All rights reserved.
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Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of Drug Competition at sigma receptors-the cases of ketamine and haloperidol.
Neurochemistry international, 2008Co-Authors: Rudie Kortekaas, R. Paul Maguire, Aren Van Waarde, Klaus L. Leenders, Philip H. ElsingaAbstract:Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for Drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [11C]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with +/- -ketamine. The tracer had a plasma half-life of 77+/-1.7min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, Ki, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands - -ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors.
Antoine Pariente - One of the best experts on this subject based on the ideXlab platform.
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A Potential Event-Competition Bias in Safety Signal Detection: Results from a Spontaneous Reporting Research Database in France
Drug Safety, 2013Co-Authors: Francesco Salvo, Florent Leborgne, Frantz Thiessard, Nicholas Moore, Bernard Bégaud, Antoine ParienteAbstract:Background In spontaneous reporting databases, reports of well-established Drug-event associations may mask alerts that arise from other Drugs (Drug Competition bias). However, a symmetrical event-Competition bias has not yet been explored whereby known events may mask an association with new events for a given Drug or Drug class. Objective The objective of this study was to explore the effects of event-Competition bias on safety signals generated from spontaneous reporting databases. Methods The Drug classes tested included statins, oral anticoagulants, antipsychotics and HIV antiretrovirals. For each, a type A reaction was selected, and its potential competitive effect on the generation of other safety signals for the Drug was explored. These were rhabdomyolysis/myopathy for statins, haemorrhage for oral anticoagulants, extrapyramidal syndrome for antipsychotics and lipodystrophy for HIV antiretrovirals. Signals of disproportionate reporting (SDRs) were detected using the case/non-case approach in the French research spontaneous reporting database (which contains reports from 1 January 1986 to 31 December 2001), before and after removing all reports concerning these competitor events. SDRs were considered as potential signals if not reported in the literature before 1 January 2002 but confirmed since. Results The whole database included 207,236 reports, 4,355 of which included statins as one of the suspected Drugs. The removal of reports of rhabdomyolysis/myopathy concerned 8,425 reports among which 867 involved statins. After this removal, 11 new SDRs appeared for statins that had not been detected initially. Similarly, 15 SDRs were unmasked for oral anticoagulants, six for antipsychotics and nine for HIV antiretrovirals. After literature-based assessment, five of the 41 unmasked SDRs appeared related to potential safety signals confirmed after 2002. Conclusion This study demonstrated that a masking phenomenon resulting from an event-Competition effect could occur when performing signal detection using disproportionality analyses of spontaneous reporting databases. This should be taken into account when routine signal detection is performed.
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A Potential Event-Competition Bias in Safety Signal Detection: Results from a Spontaneous Reporting Research Database in France
Drug safety, 2013Co-Authors: Francesco Salvo, Florent Leborgne, Frantz Thiessard, Nicholas Moore, Bernard Bégaud, Antoine ParienteAbstract:Background In spontaneous reporting databases, reports of well-established Drug-event associations may mask alerts that arise from other Drugs (Drug Competition bias). However, a symmetrical event-Competition bias has not yet been explored whereby known events may mask an association with new events for a given Drug or Drug class.
