Muscarinic Receptor Binding of the Novel Radioligand, [3H]Imidafenacin in the Human Bladder and Parotid Gland

Journal of Pharmacological Sciences

Masayuki Takeda¹  Yoshiharu Deguchi⁵  Shizuo Yamada³  Yoshihiko Ito³  Atsushi Otsuka⁴  Seiichiro Ozono⁴  Keisuke Masuyama¹  Takashi Okura⁵  Akira Yoshida³  Shiori Kuraoka³  Isao Araki² 

[1] Department of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Japan;Department of Urology, Shiga University of Medical Sciences, Japan;Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Japan;Department of Urology, Hamamatsu University School of Medicine, Japan;Laboratory of Drug Disposition & Pharmacokinetics, Faculty of PharmaScience, Teikyo University, Japan

关键词: overactive bladder;    [3H]imidafenacin;    human bladder;    parotid gland;    muscarinic receptor;   

DOI  :  10.1254/jphs.13193FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(23)Cited-By(1)The aim of the current study was to demonstrate highly specific and direct binding activity of tritium ([3H])-labeled imidafenacin for labeling muscarinic receptors in human bladder and parotid gland. Specific binding of [3H]imidafenacin in human tissues was saturable, reversible, and of high affinity. The Kd value for specific [3H]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 [3H]imidafenacin for binding sites in the human bladder and parotid gland in a concentrationdependent manner, which indicated pharmacological specificity of [3H]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. [3H]Imidafenacin may also be a useful radioligand for labeling the M3 subtype of muscarinic receptors with higher selectivity than other radioligands.

【 授权许可】

Unknown