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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1999-11-22
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pubmed:abstractText |
Several positron emission tomography (PET) radioligands based on the aryl tropane structure have been used for studies on monoamine reuptake sites. RTI-364, RTI-330, and RTI-357 (3-beta-(4'-n-propyl-,4'-iso-propyl-, and 4'-iso-propenyl-phenyl)nortropane-2-beta-carboxylic acid methyl ester) are three recently synthesized cocaine analogues with higher affinity for the serotonin (5-HTT) than the dopamine transporter (DAT). Unlabelled RTI-364 and RTI-330 were prepared in a two-step synthesis. The key step was the addition of the appropriate propyl Grignard reagent to anhydroecgonine methyl ester. RTI-357 was prepared in a three-step synthesis with a palladium-catalyzed coupling reaction of beta-CIT and isopropenylzinc bromide as key step. Hydrolysis of the ester functions gave the carboxylic acid analogues of RTI-364, RTI-330, and RTI-357, which were labelled with 11C using [11C]methyl iodide in dimethyl formamide (DMF) and tetrabutylammonium hydroxide (TBAH) as base. All three compounds entered the monkey brain in a high degree (approximately 5-10%). There was a low uptake of [11C]RTI-364 in serotonin-rich brain areas, whereas [11C]RTI-330 and [11C]RTI-357 showed a marked uptake of radioactivity in the thalamus and the brainstem, regions known to contain serotonin transporters. Transient equilibrium was reached at 15 and 40 min for [11C]RTI-330 and [11C]RTI-357, respectively. After pretreatment with citalopram, the ratio of radioactivity in the thalamus and the brainstem to the cerebellum were markedly reduced for [11C]RTI-357 but not for [11C]RTI-330. The results indicate that [11C]RTI-357 is a potential PET radioligand for quantitation of the serotonin reuptake site.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0969-8051
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pubmed:author |
pubmed-author:BesnardJ CJC,
pubmed-author:ChalonSS,
pubmed-author:ChowY NYN,
pubmed-author:DouziechLL,
pubmed-author:EmondPP,
pubmed-author:FardeLL,
pubmed-author:FranginYY,
pubmed-author:GareauLL,
pubmed-author:GuilloteauDD,
pubmed-author:HalldinCC,
pubmed-author:HelfenbeinJJ,
pubmed-author:OkuboYY,
pubmed-author:SandellJJ,
pubmed-author:SwahnC GCG
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pubmed:issnType |
Print
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
491-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10473187-Animals,
pubmed-meshheading:10473187-Binding, Competitive,
pubmed-meshheading:10473187-Brain,
pubmed-meshheading:10473187-Carbon Radioisotopes,
pubmed-meshheading:10473187-Carrier Proteins,
pubmed-meshheading:10473187-Cocaine,
pubmed-meshheading:10473187-Haplorhini,
pubmed-meshheading:10473187-Indicators and Reagents,
pubmed-meshheading:10473187-Kinetics,
pubmed-meshheading:10473187-Membrane Glycoproteins,
pubmed-meshheading:10473187-Membrane Transport Proteins,
pubmed-meshheading:10473187-Molecular Conformation,
pubmed-meshheading:10473187-Molecular Structure,
pubmed-meshheading:10473187-Nerve Tissue Proteins,
pubmed-meshheading:10473187-Organ Specificity,
pubmed-meshheading:10473187-Radioligand Assay,
pubmed-meshheading:10473187-Serotonin,
pubmed-meshheading:10473187-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:10473187-Tomography, Emission-Computed
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pubmed:year |
1999
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pubmed:articleTitle |
PET examination of three potent cocaine derivatives as specific radioligands for the serotonin transporter.
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pubmed:affiliation |
INSERM U316 Université Francois Rabelais, Tours, France.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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