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- W966704601 abstract "[O-methyl- 11 C]WAY-100635 {[O-methyl- 11 C]N-2-(1-(4-(2-methoxypheny)-l-piperazinyl)-ethyl)-N-(2-pyridyl)-cyclohexanecarboxamide} is a promising radioligand for the study of 5-HT 1A receptors in human brain with positron emission tomography (PET). Mathematical modeling of the acquired PET data requires the knowledge of radioligand metabolism. After iv injection of [O-methyl- 11 C]WAY-100635 in five healthy male volunteers, radioactivity was found to clear rapidly from plasma. Radioactivity in serial plasma samples was analyzed by solid phase extraction and reverse phase high performance liquid chromatography (HPLC) of the retained components. In all samples, a polar fraction of plasma radioactivity was not retained by the solid phase extraction column. HPLC analyses of retained radioactivity revealed three major components, of which unchanged radioligandis the least polar. Of the radioactivity in plasma, on average 94.9% was unchanged radioligand at 2.5 min after iv injection and 4.5% at 60 min. One radioactive metabolite was found to coelute with descyclohexanecarbonyl-WAY-100635 (WA Y-100634). [ 11 c]WAY-100634 represented 35% of the radioactivity in plasma at 10 min and 26% at 60 min. At 60 min, polar radioactive metabolites represented 70.5% of the radioactivity in plasma. WAY-lO0634 is known to have high affinity for 5-HT 1A and α 1 -adrenoceptors and higher extraction into rat brain than WAY-lO0635. Thus, [O-methyl- 11 C]WAY-100634 may contribute to nonspecific and specific binding in human brain in PET studies with [O-methyl- 11 C]WAY-100635. It has been conclude that WAY-100635 labeled with carbon-11 in the amido carbonyl group might be the preferred for PET studies of 5-HT 1A receptors in humans because [ 11 C]WAY-100634 cannot be formed from this radioligand." @default.
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- W966704601 date "1996-01-01" @default.
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- W966704601 title "Radioactive Metabolites of the 5-HT1A Receptor Radioligand, [O-methyl-11C]WAY-100635, in Humans" @default.
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- W966704601 doi "https://doi.org/10.1016/b978-012389760-2/50009-8" @default.
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