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