Document Detail

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.
MedLine Citation:
PMID:  19719235     Owner:  NLM     Status:  MEDLINE    
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.
Leonie Wyffels; Giulio G Muccioli; Sylvie De Bruyne; Lieselotte Moerman; Johan Sambre; Didier M Lambert; Filip De Vos
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  52     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-09-01     Completed Date:  2009-09-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4613-22     Citation Subset:  IM    
Department of Radiopharmacy, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
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MeSH Terms
Amidohydrolases / analysis*,  metabolism
Arachidonic Acids / chemical synthesis,  metabolism*
Brain / enzymology*
CHO Cells
Carbon Radioisotopes / diagnostic use
Isotope Labeling
Mice, Inbred C57BL
Polyunsaturated Alkamides / chemical synthesis,  metabolism*
Radioligand Assay
Receptor, Cannabinoid, CB1 / metabolism
Structure-Activity Relationship
Reg. No./Substance:
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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