Development of a selective and potent radioactive ligand for histamine H3 receptors: A compound potentially useful for receptor occupancy studies

Radioligands are powerful tools for examining the pharmacological profiles of chemical leads and thus facilitate drug discovery. In this study, we identified and characterized 3-(1,1,1-³H]methyl)-2-(4-{3-(1-pyrrolidinyl)propyl]oxy} phenyl)-4(3H)-quinazolinone (³H]1) as a potent and selective radioligand for histamine H₃ receptors. Radioligand ³H]1 exhibited appreciable specific signal in brain slices prepared from wild-type mice but not from histamine H₃ receptor-deficient mice, demonstrating the specificity and utility of ³H]1 as a selective histamine H₃ receptor radioligand for ex-vivo receptor occupancy assays.