Investigation of the NMDA Receptor System in Man as a Potential Surrogate Marker for Deficit Syndrome in Schizophrenia: a [123]I-CNS 1261 Single Photon Emission Tomography (SPET) Study

This study was designed to compare the [123]I-CNS 1261 binding to NMDA receptor between healthy volunteers and different subgroups of schizophrenic patients. Investigation of the potential influence of antipsychotic and concomitant medication on [123I] CNS 1261 binding is also relevant.Fifteen healthy subjects (male and female of non-child bearing potential) will be recruited and 40 schizophrenic patients divided in 3 subgroups as indicated before: Subgroup a) treatment-naive, (n=10); Subgroup b) on stable treatment with risperidone (without criteria of deficit syndrome on the SDS scale, (n=15);Subgroup c) on stable treatment with risperidone fitting criteria of deficit syndrome on the SDS scale, (n=15).

开始日期2005-07-01

申办/合作机构

GSK Plc

100 项与 CNS-1261(PAION AG) 相关的临床结果

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100 项与 CNS-1261(PAION AG) 相关的转化医学

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100 项与 CNS-1261(PAION AG) 相关的专利（医药）

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项与 CNS-1261(PAION AG) 相关的文献（医药）

2015-01-01·Bioorganic & Medicinal Chemistry Letters4区 · 医学

New N-aryl-N′-(3-(substituted)phenyl)-N′-methylguanidines as leads to potential PET radioligands for imaging the open NMDA receptor

4区 · 医学

Article

作者: Pike, Victor W ; Naumiec, Gregory R ; Cai, Lisheng

An expansive set of N-aryl-N'-(3-(substituted)phenyl)-N'-methylguanidines was prepared in a search for new leads to prospective PET ligands for imaging of the open channel of the N-methyl-d-aspartate (NMDA) receptor in vivo. The N-aryl rings and their substituents were varied, whereas the N-methyl group was maintained as a site for potential labeling with the positron-emitter, carbon-11 (t1/2=20.4min). At micromolar concentration, over half of the prepared compounds strongly inhibited the binding of [(3)H]TCP to its binding site in the open NMDA receptor in vitro. Four ligands displayed affinities that are similar or superior to those of the promising SPECT radioligand ([(123)I]CNS1261). The 3'-dimethylamino (19; Ki 36.7nM), 3'-trifluoromethyl (20; Ki 18.3nM) and 3'-methylthio (2; Ki 39.8nM) derivatives of N-1-naphthyl-N'-(phenyl)-N'-methylguanidine were identified as especially attractive leads for PET radioligand development.

2008-04-01·Psychopharmacology3区 · 医学

Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study

3区 · 医学

Article

作者: Arstad, Erik ; Teneggi, Vincenzo ; Stone, James M. ; Krystal, John H. ; Pilowsky, Lyn S. ; Erlandsson, Kjell ; Ell, Peter J. ; Squassante, Lisa ; Bressan, Rodrigo A.

RATIONALEKetamine induces effects resembling both positive and negative psychotic symptoms of schizophrenia. These are thought to arise through its action as an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor.OBJECTIVESWe used [(123)I]CNS-1261 to study ketamine binding to NMDA receptors in healthy human controls in vivo and its relationship to positive and negative psychotic symptom induction.MATERIALS AND METHODSTen healthy controls underwent two single-photon emission tomography scans with [(123)I]CNS-1261. On each occasion, they received a bolus infusion of either ketamine or saline. The Brief Psychiatric Rating Scale (BPRS) was administered at the end of each scan. Predefined regions of interest were used to estimate change in volume of distribution of [(123)I]CNS-1261 following ketamine administration. Two normalised-to-cortex binding indices were also used in order to study effects of ketamine on NMDA receptor availability by region, after correction for global and nonspecific effects.RESULTSKetamine-induced reduction in [(123)I]CNS-1261 volume of distribution in all regions showed the strongest correlation with BPRS negative subscale (p < 0.01). With the normalised-to-cortex measures, NMDA receptor binding in middle inferior frontal cortex showed a significant correlation with BPRS negative subscale (BI1 r = 0.88, BI2 r = 95.9, p < 0.001).CONCLUSIONS[(123)I]CNS-1261 binding was modulated by ketamine, a drug known to compete for the same site on the NMDA receptor in vitro. Ketamine may induce negative symptoms through direct inhibition of the NMDA receptor, and positive symptoms may arise through a different neurochemical pathway.

2006-02-01·Molecular Psychiatry1区 · 医学

First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients

1区 · 医学

Letter

作者: K Erlandsson ; Lyn Pilowsky ; PJ Ell ; James Stone ; JH Krystal ; RS Mulligan ; Rodrigo Affonseca Bressan

The hypothesis suggesting a deficit in NMDA receptor function which is underlying cause for schizophrenia was tested using the highly selective single photon emission tomog. NMDA receptor tracer, ^[123]CNS-1261.^[123]CNS-1261 is an intrachannel NMDA receptor SPET probe that has been extensively developed with quant. kinetic modeling methods in humans.Comparison of BI₂ data using SPM99 revealed a single cluster of decreased binding in drug free schizophrenic patients compared with normal volunteers centered around a point corresponding to left uncus (hippocampus).ANOVA of the ROI-based data revealed that the hippocampus, superior frontal and posterior cerebral regions showed significant differences by group.NMDA receptor binding in the hippocampus relative to whole cortex was significantly lower in drug free patients compared to healthy volunteers and in drug-free patients compared to typical antipsychotic treated patients.

100 项与 CNS-1261(PAION AG) 相关的药物交易

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