title: Muscarinic receptor binding of the novel radioligand, [3h]imidafenacin in the human bladder and parotid gland.
abstract: The aim of the current study was to demonstrate highly specific and direct binding activity of tritium ([(3)H])-labeled imidafenacin for labeling muscarinic receptors in human bladder and parotid gland. Specific binding of [(3)H]imidafenacin in human tissues was saturable, reversible, and of high affinity. The Kd value for specific [(3)H]imidafenacin binding in the human bladder was approximately 3 times higher than that in the parotid gland. Unlabeled imidafenacin as well as the clinically used antimuscarinic agents, oxybutynin, tolterodine, and solifenacin, competed with [(3)H]imidafenacin for binding sites in the human bladder and parotid gland in a concentrationdependent manner, which indicated pharmacological specificity of [(3)H]imidafenacin binding sites. The Ki for imidafenacin in the human bladder approximately corresponded to pharmacological potency for the competitive blockade of carbachol-induced contractions of bladder, indicating a close correlation between binding affinity of imidafenacin to bladder muscarinic receptors and its pharmacological effects in the bladder. In conclusion, the current study is the first to provide direct evidence to demonstrate that imidafenacin bound muscarinic receptors in the human bladder, supporting its clinical relevance as a therapeutic agent for overactive bladder. [(3)H]Imidafenacin may also be a useful radioligand for labeling the M3 subtype of muscarinic receptors with higher selectivity than other radioligands.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.forename: Shiori
authors.initials: S
authors.lastname: Kuraoka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Okura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Deguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
authors.forename: Isao
authors.initials: I
authors.lastname: Araki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000378:metabolism*; D011869:Radioligand Assay; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D013194:Staining and Labeling; D014316:Tritium; D001743:Urinary Bladder / Q000378:metabolism*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
chemical_list: D007093:Imidazoles; D043587:Receptor, Muscarinic M3; D014316:Tritium; C120953:imidafenacin