Abstract |
Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C] Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C] pimavanserin is not selective for the 5-HT2AR in pigs.
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Authors | Valdemar L Andersen, Hanne D Hansen, Matthias M Herth, Agnete Dyssegaard, Gitte M Knudsen, Jesper L Kristensen |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 25
Issue 5
Pg. 1053-6
(Mar 01 2015)
ISSN: 1464-3405 [Electronic] England |
PMID | 25655720
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Carbon Radioisotopes
- Ligands
- Piperidines
- Radiopharmaceuticals
- Receptor, Serotonin, 5-HT2A
- Serotonin 5-HT2 Receptor Agonists
- Urea
- pimavanserin
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Topics |
- Animals
- Carbon Radioisotopes
(analysis, metabolism)
- Ligands
- Methylation
- Piperidines
(analysis, metabolism)
- Positron-Emission Tomography
- Radiopharmaceuticals
(analysis, metabolism)
- Receptor, Serotonin, 5-HT2A
(analysis, metabolism)
- Serotonin 5-HT2 Receptor Agonists
(analysis, metabolism)
- Swine
- Urea
(analogs & derivatives, analysis, metabolism)
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