title: Muscarinic Receptor Binding of Imidafenacin in the Human Bladder Mucosa and Detrusor and Parotid Gland.
abstract: OBJECTIVE
  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 [(3) H]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) Kd values for [(3) H]NMS binding in the human detrusor muscle and parotid gland, with little effect on Bmax values. This observation indicates that imidafenacin binds to the muscarinic receptors in human tissues in a competitive and reversible manner.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Seki
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ogoda
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Kuraoka
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Masuyama
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Araki
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, JapanDepartment of Urology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Urology and Otolaryngology, School of Medicine, University of Yamanashi, Chuo, JapanDepartment of Urology, Shiga University of Medical Science, Ohtsu, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
keywords: detrusor; human bladder mucosa; imidafenacin; muscarinic receptor; parotid gland