Muscarinic Receptor Binding of Imidafenacin in the Human Bladder Mucosa and Detrusor and Parotid Gland

作者：Seki Masanao; Ogoda Masaki; Kuraoka Shiori; Otsuka Atsushi; Ozono Seiichiro; Takeda Masayuki; Masuyama Keisuke; Araki Isao; Yamada Shizuo^*

来源：Lower Urinary Tract Symptoms, 2011, 3(2): 64-68.

DOI：10.1111/j.1757-5672.2011.00089.x

• detrusor
• human bladder mucosa
• imidafenacin
• muscarinic receptor
• parotid gland

Objectives: The current study aimed to characterize comparatively the binding of imidafenacin to muscarinic receptors in the human bladder mucosa and detrusor muscle and parotid gland.
Methods: The muscarinic receptor in homogenates of human tissues (bladder mucosa and detrusor muscle and parotid gland) was measured using a radioligand binding assay with [N-methyl-(3)H] scopolamine methyl chloride ([(3)H]NMS).
Results: Imidafenacin competed with [3H] NMS for binding sites in the bladder mucosa and detrusor muscle and parotid gland, and its affinity was significantly (2.6-8.7 times) higher than that of oxybutynin. Also, the affinity of imidafenacin for muscarinic receptors was approximately two-fold higher in the parotid gland than bladder tissue. The affinity of imidafenacin in the mucosa was similar to that in the detrusor muscle, suggesting that this agent exhibits therapeutic effects by blocking muscarinic receptors in the mucosa as well as detrusor muscle. Scatchard analysis revealed that imidafenacin increased significantly (approximately four-fold) K(d) values for [(3)H] NMS binding in the human detrusor muscle and parotid gland, with little effect on B(max) values. This observation indicates that imidafenacin binds to the muscarinic receptors in human tissues in a competitive and reversible manner.
Conclusion: Imidafenacin binds to muscarinic receptors in the human bladder mucosa and detrusor muscle and parotid gland with high affinity. This agent was considered to exhibit therapeutic effects on the lower urinary tract symptoms due to an overactive bladder by blocking muscarinic receptors in the urothelium as well as detrusor muscle.

• 出版日期2011-9