Document Detail

An iodinated derivative of moclobemide as potential radioligand for brain MAO-A exploration.
MedLine Citation:
PMID:  8614267     Owner:  NLM     Status:  MEDLINE    
In vivo evaluation of MAO-A would be of great value for the diagnosis and follow-up of therapy of depression. In order to perform this exploration by SPECT, we developed an iodinated derivative of the reversible MAO-A inhibitor, moclobemide. Ro 11-9900 was synthesized and analysed by IR, NMR and HPLC. Radioiodination was carried out by nucleophilic exchange of [125I] on the brominated precursor, and yielded [125I]-Ro 11-9900 with high specific activity. In vitro experiments on rat brain homogenates showed that Ro 11-9900 had poor inhibitory activity on MAO-A, as already described for moclobemide. By contrast, in vivo biodistribution in the rat brain showed that [125I]-Ro 11-990 accumulated in a region corresponding to the localization of locus coeruleus known for its high density of MAO-A. Moreover, preinjection of the irreversible MAO-A inhibitor clorgyline (10 prevented accumulation of radioactivity by 40 to 60% and we found that the radioactivity in the brain corresponded exclusively to [125I]-Ro 11-9900 and not to a metabolite. [125I]-Ro 11-9900 was highly accumulated in the pineal gland, both on MAO-A and on MAO-B sites. We concluded that the unmetabolized iodinated derivative of moclobemide, Ro 11-9900, preferentially labeled MAO-A in vivo in the rat brain. This compound would therefore be a potential tracer for evaluation of MAO-A by SPECT.
H Rafii; S Chalon; J E Ombetta; Y Frangin; L Pourcelot; J C Besnard; S Bodard; D Guilloteau
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Life sciences     Volume:  58     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1996  
Date Detail:
Created Date:  1996-06-05     Completed Date:  1996-06-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1159-69     Citation Subset:  IM    
INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, Tours, France.
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MeSH Terms
Benzamides / chemical synthesis*,  metabolism,  pharmacology*
Brain / enzymology*,  metabolism,  radionuclide imaging
Chromatography, High Pressure Liquid
Iodine Radioisotopes / diagnostic use*
Isoenzymes / analysis*,  antagonists & inhibitors
Isotope Labeling
Magnetic Resonance Spectroscopy
Monoamine Oxidase / analysis*
Monoamine Oxidase Inhibitors / pharmacology
Radioligand Assay
Rats, Wistar
Sensitivity and Specificity
Spectrophotometry, Infrared
Tissue Distribution
Tomography, Emission-Computed, Single-Photon
Reg. No./Substance:
0/Benzamides; 0/Iodine Radioisotopes; 0/Isoenzymes; 0/Monoamine Oxidase Inhibitors; 64544-20-3/4-iodo-N-(2-(4-morpholinyl)ethyl)benzamide; 71320-77-9/Moclobemide; EC Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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