Abstract
Radioligands used previously for histamine H-3 receptor (H3R) are accompanied by a number of disadvantages. In this study, we report the synthesis of the new H3R radioligand [H-3]UR-MN259 ([H-3]<bold>11</bold>) with high (radio)chemical purity and stability. The radioligand exhibits sub-nanomolar affinity for the target receptor (pK(i) (H3R) = 9.56) and displays an outstanding selectivity profile ...
Abstract
Radioligands used previously for histamine H-3 receptor (H3R) are accompanied by a number of disadvantages. In this study, we report the synthesis of the new H3R radioligand [H-3]UR-MN259 ([H-3]<bold>11</bold>) with high (radio)chemical purity and stability. The radioligand exhibits sub-nanomolar affinity for the target receptor (pK(i) (H3R) = 9.56) and displays an outstanding selectivity profile within the histamine receptor family (>100,000-fold selective). [H-3]UR-MN259 is ideally suitable for the characterization of H3R ligands in competition binding and shows one-site binding to the H3R in saturation binding experiments. The radiotracer shows fast association to the receptor (tau(assoc) = 6.11 min), as well as full dissociation from the receptor (tau(dissoc) = 14.48 min) in kinetic binding studies. The distinguished profile of [H-3]UR-MN259 makes it a highly promising pharmacological tool to further investigate the role of the H3R in the CNS.
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