Development of a selective and potent radioactive ligand for histamine H(3) 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-(3)H]methyl)-2-(4-{[3-(1-pyrrolidinyl)propyl]oxy} phenyl)-4(3H)-quinazolinone ([(3)H]1) as a potent and selective radioligand for histamine H(3) receptors. Radioligand [(3)H]1 exhibited appreciable specific signal in brain slices prepared from wild-type mice but not from histamine H(3) receptor-deficient mice, demonstrating the specificity and utility of [(3)H]1 as a selective histamine H(3) receptor radioligand for ex-vivo receptor occupancy assays.