PMID: 11323236Apr 27, 2001Paper

Synthesis and evaluation of racemic [(11)C]NS2456 and enantiomers as selective serotonin reuptake radiotracers for PET

Nuclear Medicine and Biology
D F SmithA Gjedde

Abstract

Positron emission tomography (PET) radiotracers are needed for quantifying serotonin uptake sites in the living brain. Therefore, we evaluated a new selective serotonin reuptake inhibitor, NS2456, to determine whether it is suited for use in PET. Racemic NS2456 [(1RS,5SR)-8-methyl-3-[4-trifluoromethoxyphenyl]-8-azabicyclo [3.2.1]oct-2-ene] and its N-demethylated analog, racemic NS2463, selectively inhibited serotonin uptake in rat brain synaptosomes; their IC(50) values were 3000-fold lower for [(3)H]serotonin than for either [(3)H]dopamine or [(3)H]noradrenaline. The enantiomers of NS2463 were also potent inhibitors of serotonin uptake in vitro, but they failed to show stereoselectivity. Racemic NS2463 as well as its enantiomers were radiolabelled by N-methylation with C-11, yielding [(11)C]NS2456 for use in PET of the living porcine brain. The compounds crossed the blood-brain barrier rapidly and accumulated preferentially in regions rich in serotonin uptake sites (e.g., brainstem, subthalamus and thalamus). However, their binding potentials were relatively low and no stereoselectivity was found. Thus, neither racemic [(11)C]NS2456 nor its [(11)C]-labelled enantiomers are ideal for PET neuroimaging of neuronal serotonin uptak...Continue Reading

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Jan 7, 2000·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·D F Smith
Aug 24, 2001·Nuclear Medicine and Biology·D F SmithA Gjedde
Aug 16, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·William B MathewsZsolt Szabo

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Citations

Sep 5, 2002·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Katalin MarthiDonald F Smith
Apr 21, 2007·Neuroscience and Biobehavioral Reviews·Nanna Marie LindAxel K Hansen
Mar 21, 2007·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Donald F Smith, Steen Jakobsen
Oct 22, 2020·Journal of Chromatography. a·Mohammad Mahdi Moein, Thuy A Tran

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