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.
Mitobe
Yuko
Y
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co., Ltd, 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan.
Ito
Sayaka
S
Mizutani
Takashi
T
Nagase
Tsuyoshi
T
Sato
Nagaaki
N
Tokita
Shigeru
S
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry; D018100:Receptors, Histamine H3 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D018435:ATP Binding Cassette Transporter, Subfamily B; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D018100:Receptors, Histamine H3