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- McNab, F, et al.
(författare)
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Changes in cortical dopamine D1 receptor binding associated with cognitive training
- 2009
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 323:5915, s. 800-802
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Tidskriftsartikel (refereegranskat)abstract
- Working memory is a key function for human cognition, dependent on adequate dopamine neurotransmission. Here we show that the training of working memory, which improves working memory capacity, is associated with changes in the density of cortical dopamine D1 receptors. Fourteen hours of training over 5 weeks was associated with changes in both prefrontal and parietal D1 binding potential. This plasticity of the dopamine D1 receptor system demonstrates a reciprocal interplay between mental activity and brain biochemistry in vivo.
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- Talvik, M, et al.
(författare)
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A cross-validation study on the relationship between central D-2 receptor occupancy and serum perphenazine concentration
- 2004
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Ingår i: Psychopharmacology. - Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Glostrup Univ Hosp, Dept Clin Biochem, Glostrup, Denmark. : SPRINGER. - 0033-3158 .- 1432-2072. ; 175:2, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: There is a need for laboratory measures to guide clinical treatment with antipsychotic drugs. For serum concentration of the classical antipsychotic drug perphenzine an optimal therapeutic interval has been identified between 2 and 6 nmol/l. Positron emission tomography (PET) studies have suggested an optimal interval in central dopamine D-2 receptor occupancy of between 65 and 80%. Objectives: The aim of the present cross-validation study in clinically stable schizophrenic patients was to examine the relationship between the optimal interval in central D-2 receptor occupancy and the therapeutic window for serum perphenazine concentration. Methods: Six patients who had responded to maintenance treatment with perphenazine decanoate were examined with PET and [C-11]raclopride during steady-state conditions. Blood sampling was carried out for minimum serum perphenazine concentration and during the PET examination. Results: The serum perphenazine concentration was between 1.8 and 9 nmol/l and the D-2 receptor occupancy varied between 66 and 82%. The relationship between central receptor occupancy and serum drug concentration was curvilinear. Mild extrapyramidal symptoms were present in the patient with the highest D-2 receptor occupancy. Conclusions: The previously suggested therapeutic window in serum perphenazine concentration is in good agreement with the optimal interval suggested for central D-2 receptor occupancy. Serum concentrations at low dose levels may therefore serve as a useful tool in clinical monitoring of antipsychotic drug treatment.
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- Plaven-Sigray, Pontus, et al.
(författare)
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Accuracy and reliability of [C-11]PBR28 specific binding estimated without the use of a reference region
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 188, s. 102-110
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Tidskriftsartikel (refereegranskat)abstract
- [C-11]PBR28 is a positron emission tomography radioligand used to examine the expression of the 18 kDa translocator protein (TSPO). TSPO is located in glial cells and can function as a marker for immune activation. Since TSPO is expressed throughout the brain, no true reference region exists. For this reason, an arterial input function is required for accurate quantification of [C-11]PBR28 binding and the most common outcome measure is the total distribution volume (V-T). Notably, V-T reflects both specific binding and non-displaceable binding. Therefore, estimates of specific binding, such as binding potential (e.g. BPND) and specific distribution volume (V-S) should theoretically be more sensitive to underlying differences in TSPO expression. It is unknown, however, if unbiased and accurate estimates of these outcome measures are obtainable for [C-11]PBR28. The Simultaneous Estimation (SIME) method uses time-activity-curves from multiple brain regions with the aim to obtain a brain-wide estimate of the non-displaceable distribution volume (V-ND), which can subsequently be used to improve the estimation of BPND and V-S. In this study we evaluated the accuracy of SIME-derived V-ND, and the reliability of resulting estimates of specific binding for [C-11]PBR28, using a combination of simulation experiments and in vivo studies in healthy humans. The simulation experiments, based on data from 54 unique [C-11]PBR28 examinations, showed that V-ND values estimated using SIME were both precise and accurate. Data from a pharmacological competition challenge (n = 5) showed that SIME provided V-ND values that were on average 19% lower than those obtained using the Lassen plot, but similar to values obtained using the Likelihood-Estimation of Occupancy technique. Test-retest data (n = 11) showed that SIME-derived V-S values exhibited good reliability and precision, while larger variability was observed in SIME-derived BPND values. The results support the use of SIME for quantifying specific binding of [C-11]PBR28, and suggest that V-S can be used in complement to the conventional outcome measure V-T. Additional studies in patient cohorts are warranted.
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- Varnas, K, et al.
(författare)
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A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers
- 2013
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Ingår i: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 33:10, s. 853-860
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administration of the antimigraine drug zolmitriptan. Methods Positron emission tomography (PET) studies were undertaken using the radioligand [11C]AZ10419369 in eight control subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examined after two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart. Two of the subjects were subsequently examined after administration of 5 mg zolmitriptan. One week after the last administration of zolmitriptan five of the subjects underwent additional PET measurements without drug pretreatment. Results After administration of 10 mg zolmitriptan, mean receptor occupancy was 4–5%. No consistent changes in 5-HT1B receptor binding were observed for subjects who received 5 mg zolmitriptan. There was a statistically significant negative relationship between binding potential ( BPND) and plasma concentration of zolmitriptan and the active metabolite 183C91, respectively. All of the five subjects who were examined 1 week after dosing with zolmitriptan showed higher BPND post drug administration compared with baseline. Conclusion This is the first demonstration of CNS 5-HT1B receptor occupancy of a triptan. The findings are consistent with the low receptor occupancy previously reported in PET studies with agonists at other G protein coupled receptors.
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