| Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain. | |
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MedLine Citation:
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PMID: 19719235 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fatty acid amide hydrolyase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids in the brain. Imaging FAAH in vivo using PET or SPECT is important to deeper understanding of its role in neuropsychiatric disorders. However, at present, no radioligand is available for mapping the enzyme in vivo. Here, we synthesized 18 aryl analogues of anandamide, FAAH's endogenous substrate, and in vitro evaluated their potential as metabolic trapping tracers. Interaction studies with recombinant FAAH revealed good to very good interaction of the methoxy substituted aryl anandamide analogues 17, 18, 19, and 20 with FAAH and they were identified as competing substrates. Compounds 17 and 18 did not display significant binding to CB1 and CB2 cannabinoid receptors and stand out as potential candidate metabolic trapping tracers. They were successfully labeled with 11C in good yields and high radiochemical purity and displayed brain uptake in C57BL/6J mice. Radioligands [11C]-17 and [11C]-18 merit further investigation in vivo. |
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Authors:
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Leonie Wyffels; Giulio G Muccioli; Sylvie De Bruyne; Lieselotte Moerman; Johan Sambre; Didier M Lambert; Filip De Vos |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 52 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-09-01 Completed Date: 2009-09-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 4613-22 Citation Subset: IM |
Affiliation:
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Department of Radiopharmacy, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amidohydrolases
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analysis*,
metabolism Animals Arachidonic Acids / chemical synthesis, metabolism* Brain / enzymology* CHO Cells Carbon Radioisotopes / diagnostic use Cricetinae Cricetulus Isotope Labeling Male Mice Mice, Inbred C57BL Polyunsaturated Alkamides / chemical synthesis, metabolism* Radioligand Assay Receptor, Cannabinoid, CB1 / metabolism Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Carbon Radioisotopes; 0/Polyunsaturated Alkamides; 0/Receptor, Cannabinoid, CB1; 94421-68-8/anandamide; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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